Serum-manganese-superoxide dismutase: normal values and increased levels in patients with acute myocardial infarction and several malignant diseases determined by an enzyme-linked immunosorbent assay using a monoclonal antibody

An enzyme-linked immunosorbent assay (ELISA) has been developed for human manganese-superoxide dismutase (Mn-SOD), using a specific monoclonal antibody raised against the purified enzyme. The Mn-SOD molecule comprises four identical sub-units and this permitted the development of a symmetrical assay, using the same monoclonal antibody as both capture and detector. The assay offers a specific, sensitive and convenient means of measuring immunoreactive Mn-SOD in human sera. Under optimum conditions, the sensitivity of the assay permits the detection of 2-200 ng of purified Mn-SOD from human liver. The mean serum Mn-SOD levels of normal healthy males and females were 99.8 +/- 24.8 (mean +/- SD) and 88.8 +/- 20.8 (mean +/- SD), respectively. A high level of the enzyme was found in the sera of patients with acute myocardial infarction as well as malignant diseases such as acute myeloid leukemia, primary hepatoma and gastric cancer. This is the first report of an ELISA using a monoclonal antibody specific for a distinct epitope of Mn-SOD.     

MORPHOLOGICAL AND BIOCHEMICAL STUDIES OF A CASE OF MUCOPOLYSACCHARIDOSIS II (HUNTER'S SYNDROME)

An autopsy case of a 19-year-old boy who had shown typical gargoyle features, strictly consistent with mucopolysaccharidosis type II (Hunter's syndrome) was reported. Histologically, cytoplasmic vacuolar change was found In hepatocytes, sinusoidal epithelium of spleen, follicular cells of thyroid, Sertoli cells of testis, chromophobe cell of pituitary and generalized fibroblast-like cells including meninges, cardiac valve and periosteum. The vacuoles consisting of membrane-bound structures with flocculus protein-like material and occasional electron dense bodies on electron microscopy, were considered to be the site of mucopolysaccharide deposition by histochemical analysis. Deposition of lipid material consistent with so-called membranous cytoplasmic body was observed in the neurons of central, peripheral and autonomic nervous system. Hepatosplenomegaly could be explained by cytoplasmic deposition, but the cause of cardiomegaly remained further to be studied. Biochemically hepatic mucopolysaccharide was identified as heparan sulfate, while in the kidney dermatan sulfate and heparan sulfate were detected. The correlation between morphology and biochemistry, and between deposition and degeneration was discussed.     

Pneumocystis carinii carriage in immunocompromised patients with and without human immunodeficiency virus infection

Eighty-one bronchoalveolar lavage (BAL) specimens obtained from 26 HIV-infected, 45 non-HIV immunosuppressed and 10 immunocompetent patients with primary pulmonary diseases were analysed for the presence of Pneumocystis carinii by staining and by P. carinii 5S rDNA determined by PCR. P. carinii was observed by staining of BAL specimens from HIV-infected patients significantly more frequently than those from immunocompromised hosts without HIV infection (57.7% versus 20.0%, respectively). P. carinii 5S rDNA was detected by PCR assay in seven (26.9%) HIV-infected individuals, which was significantly more frequent than for four (8.9%) immunosuppressed patients without HIV infection, for whom staining was negative. None of these patients developed P. carinii pneumonia (PCP) within the follow-up period. BAL specimens from 10 immunocompetent patients with pulmonary disorders were negative for PCP by both staining and PCR assay.     

Adrenalectomy increases local cerebral blood flow in the rat hippocampus

The present study examined the effect of glucocorticoid manipulations on local cerebral blood flow in the hippocampus. We measured local cerebral blood flow in the hippocampus at 1-h intervals over a 1-day period in freely moving rats, by means of the H₂ clearance method, before and after sham adrenalectomy, adrenalectomy or adrenalectomy with corticosterone replacement. We also measured local cerebral blood flow in the prefrontal cortex before and after adrenalectomy. Four weeks after the adrenalectomy, hippocampal blood flow at each time of day was an average of 47% greater than before the operation, showing diurnal variation as before. After the sham adrenalectomy or adrenalectomy with corticosterone replacement, hippocampal blood flow did not change significantly with respect to either its level or its diurnal variation. Local cerebral blood flow in the prefrontal cortex increased by only 19% after adrenalectomy. The present study demonstrates that adrenalectomy causes a remarkable increase in hippocampal blood flow, probably due to a lack of corticosterone.     

Generators of visual evoked potentials for faces and eyes in the human brain as determined by dipole localization

Human visual evoked potentials were recorded during presentation of photos of human and animal faces and various face features. Negative waves with approximate peak latencies of 165 msec (N170) were bilaterally recorded from the occipito-temporal regions. Mean peak latencies of the N170 were shorter for faces than eyes only. Analyses of amplitudes of evoked potentials indicated that the N170 elicited by faces reflected activity of a specific neural system which was insensitive to detailed differences among individual faces regardless of species, and consequently suggest that this system might function to detect existence of faces in general. On the other hand, the mean amplitude of the N170 elicited by human eyes was significantly larger than those by animal eyes. These differences in response latencies and amplitudes of the N170 suggest existence of at least 2 different visual evoked potentials with similar latencies (i.e., N170) which are sensitive to faces in general and human eyes, respectively. Dipole source localization analysis indicated that dipoles for the N170 elicited by eyes were located in the posterior inferior temporal gyrus, and those for faces, located initially in the same region, but moved toward the fusiform and lingual gyri at the late phase of the N170. The results indicated that information processing of faces and eyes separated at least as early as the latency of the N170 at the posterior inferior temporal gyrus as well as the fusiform and lingual gyri, and might provide neurophysiological and anatomical bases to an initial structural encoding stage of human faces.     

3-Nitropropionic acid preconditioning ameliorates delayed neurological deterioration and infarction after transient focal cerebral ischemia in gerbils

The effect of 3-nitropropionic acid (3-NP), a selective inhibitor of succinic dehydrogenase, preconditioning on postischemic neurological deterioration and infarction was examined in gerbils after transient ischemia. The animals were pretreated with 1-80mg/kg of 3-NP 1 day before ischemia induced by two 10-min occlusions of the left common carotid artery. Four milligrams per kilogram 3-NP pretreatment significantly ameliorated postischemic neurological deterioration (stroke index at 7 days postischemia, 1.4+/-1.5 vs. 7.4+/-5.4 in 4 mg/kg-pretreated vs. non-pretreated animals: mean+/-SD) and reduced infarct volume (24+/-4.8 vs. 43+/-12 mm(3)). One and 20 mg/kg 3-NP induced milder neuroprotection, and 80 mg/kg 3-NP aggravated postischemic stroke symptoms and infarction. Thus, appropriate doze of 3-NP preconditioning is effective in ameliorating the postischemic neurological deterioration and reducing infarct volume.     

The frequency of patients with positive HIV-antibody in the various groups and the prognosis of these patients treated with SNMC

Among 300 patients receiving blood and/or blood products because of blood disorders, 3 (1%) were positive for HIV by ELISA. However, 3 patients were thought to be false positive because they had received bolus injection of gamma-globulin and their serum became negative after 6 months. Moreover, no viral inclusion or HIV-antigen was detected. In 30 patients with hemophilia and related disorders, 21 (70%) were positive by ELISA, Immunofluorescence, Passive-agglutination and Western Blot method. Immunodeficiency, as reflected by decreases of CD 4/8 ratio and NK activity, was successfully treated with high-dose of Stronger Neo-Minophagen C.     

Intergenerational instability of the CAG repeat of the gene for Machado- Joseph disease (MJD1) is affected by the genotype of the normal chromosome: implications for the molecular mechanisms of the instability of the CAG repeat

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at 14q32.1. To identify elements affecting the intergenerational instability of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the CAG repeat affects intergenerational instability of the CAG repeat. The [expanded (CAG)n-CGG]/[normal (CAG)n- GGG] haplotypes were found to result in significantly greater instability of the CAG repeat compared to the [expanded (CAG)n- CGG]/[normal (CAG)n-CGG] or [expanded (CAG)nGGG]/[normal (CAG)n-GGG] haplotypes. Multiple stepwise logistic regression analysis revealed that the relative risk for a large intergenerational change in the number of CAG repeat units (< -2 or > 2) is 7.7-fold (95% CI: 2.5-23.9) higher in the case of paternal transmission than in that of maternal transmission and 7.4-fold (95% CI: 2.4-23.3) higher in the case of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes than in that of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The combination of paternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes resulted in a 75.2-fold (95% CI: 9.0-625.0) increase in the relative risk compared with that of maternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The results suggest that an inter- allelic interaction is involved in the intergenerational instability of the expanded CAG repeat.      

Frequency-to-voltage conversion in the pyramidal tract neuron: an important role of the inhibitory postsynaptic potential

Frequency-coded impulses are known to be converted into postsynaptic potentials (PSPs) at the synapse of a target neuron. This can be termed frequency-voltage (F-V) conversion. Studies on this problem in pyramidal tract neurons (PTNs) showed that not only the amplitude but also the duration of depolarizing PSPs was determined as a function of the input impulse frequency. Two opposite patterns of F-V conversion were observed following activation of two input systems to PTNs. Inhibitory postsynaptic potentials were found to play an important role in the regulation of the duration of PSPs by curtailing excitatory post-synaptic potentials.