Neuronal expression of nuclear and mitochondrial genes for cytochrome oxidase (CO) subunits analyzed by in situ hybridization: comparison with CO activity and protein.

Cytochrome oxidase (CO) is a mitochondrial energy-generating enzyme of the oxidative phosphorylation pathway. In neurons, CO activity varies among different cells and compartments (perikarya, dendrites, axons, and terminals) according to their physiological activity and metabolic requirements. Regulation of enzyme protein levels, rather than enzyme turnover number, largely accounts for local variations in CO activity (Hevner and Wong-Riley, 1989, 1990). In the present study, we examined how CO activity and protein levels are related to mitochondrial DNA (mtDNA) and CO subunit mRNA levels in neurons and neuronal compartments. Mammalian CO comprises 13 subunits (Kadenbach et al., 1983), of which three are encoded in mtDNA and 10 in nuclear genes. We studied one mitochondrial-encoded mRNA [subunit I (COI)], two nuclear-encoded mRNAs (COIV, COVIII), and mtDNA, using in situ hybridization to determine their distributions in monkey hippocampus, cerebellum, and primary visual cortex. We compared their distributions with those of CO activity and protein, determined by histochemistry and immunohistochemistry, respectively. In all regions, the local content of mtDNA was similar, but not identical, to the activity and amount of CO. Expression of COI mRNA was not proportional to mtDNA abundance or CO activity and protein, but instead was highest in cell bodies, lower in dendrites, and undetectable in axon terminals. COIV and COVIII mRNAs were detected exclusively in perikarya and proximal dendrites. Thus, the nuclear-encoded subunits of CO are probably translated mainly in neuronal cell bodies and allocated to other compartments posttranslationally. Regulation of CO was studied in two monkeys treated by monocular tetrodotoxin (TTX) injection, a procedure that blocks impulses from one eye. In those animals, cortical changes in CO activity were correlated with changes in mtDNA and in COI, COIV, and COVIII mRNA. Our results suggest that neuronal CO is synthesized and assembled mainly in cell bodies and indicate that both nuclear and mitochondrial CO subunit genes are regulated by neuronal activity.     

In vivo and in vitro studies on modulation of the pineal endocrine function by L-acetyl-carnitine in the rat.

Male Sprague-Dawley rats injected (i.p.) at 1500h with L-acetyl-carnitine in doses of 10, 30 or 90 mg/kg exhibited a notable increase in their pineal and serum melatonin content 1 hr later. Likewise, L-acetyl-carnitine administered in the same dose range induced a significant increase of pineal and serum melatonin content in rats treated at 0100h, following exposure of 30 min to bright white light to suppress endogenous melatonin. Under in vitro experimental conditions, however, 60 min of coincubation of isolated rat pineal glands with L-acetyl-carnitine (10(-5) M) did not result in an elevation in melatonin accumulated in the incubation medium. These results demonstrate that, in vivo, L-acetyl-carnitine can exert a modulatory action on synthesis and release of melatonin, possibly by modifying noradrenergic transmission and signal transduction in the pineal gland.     

Psychiatric aspects of head and neck surgery. Part I: New surgical techniques and psychiatric consequences.

Individuals who undergo head and neck surgery experience extreme stressors that go beyond those which occur with the usual surgical patient. This paper will review the literature and discuss the psychiatric consequences of otolaryngeal surgery. In addition, new head and neck surgical techniques, which offer special challenges to the patient as well as to the psychiatric consultant, will be examined. Tracheostomy, which occurs as a result of head and neck surgery, is of particular importance with regard to postoperative adaptation and is a significant complication that must be reckoned with.     

Effect of psychotomimetics and some putative anxiolytics on stress-induced hyperthermia

Summary Stress-induced hyperthermia (SIH), which is seen in the last mice removed from the cage, is a novel animal model sensitive to anxiolytic drugs. SIH is antagonized by CL 218872 (25 and 50 mg/kg, os), by tracazolate (5 and 7.5 mg/kg, ip) and by 2-AP-5 (50 and 100 mg/kg, ip). At higher dose, CL 218872 (100 mg/kg, os) and tracazolate (12.5 mg/kg, ip) lose their activity.PK 9084 (5–40 mg/kg, ip) and CGS 9896 (2–20 mg/kg, both ip and os) were also ineffective in preventing SIH. The anti-hyperthermic effect of CL 218872 (25 mg/kg) and tracazolate (7.5 mg/kg) was blocked by the benzodiazepine antagonist Ro 15–1788 (15 mg/kg). CGS 9896 (10 mg/kg, os) also reversed the effect of CL 218872 (25 mg/kg) on SIH.Differently from anxiolytics, MK-801 (0.5–1 mg/kg, os), PCP (2.5 mg/kg, ip) and d-amphetamine (10 mg/kg, ip) evoked hyperthermia in the first set of mice and prevented a further stress-induced rise of body temperature in the last set of mice.     

The determination of alpha-tocopherol in blood serum]

A modified method for measuring vitamin E is described, making use of thin-layer chromatography with Silufol plates. Effects of various storage conditions of the blood serum on its vitamin E levels were examined. Vitamin E proved to be sufficiently stable at storage at -10 degrees C and defrosting under 20 degrees C. Comparison of this mode of storage with other ones has demonstrated its advantages. The method was tried in clinical practice in examinations of patients with pulmonary tuberculosis, chronic alcoholism, females suffering from infertility due to inflammations and healthy ones (controls) and found to be accurate, reproducible, and informative.     

Biologic variation of common hematologic laboratory quantities in the elderly

Analytic, within-subject, and between-subject biologic variations were estimated for leukocytes, erythrocytes, hemoglobin, hematocrit, mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin content (MCHC), platelets, and a three-component differential count (lymphocytes, monocytes, and granulocytes in terms of both concentration and percentage of leukocytes) in cohorts of 12 male and 12 female healthy elderly subjects. The assays were performed with an Ortho ELT-800 automated analyzer. The estimates of within-subject biologic variation were similar to published data on young subjects, indicating that this aspect of homeostasis is not compromised in the elderly. The data were used to derive objective analytic goals; goals were surpassed except for assays of erythrocytes, hematocrit, and the derived MCV, MCH, and MCHC. The changes required for serial results to be significantly different were determined and found to be generally valid because most quantities have no heterogeneity of within-subject variation. All quantities had significant individuality; in consequence, conventional population-based reference values are of limited utility, and screening using reference limits will not detect latent or early disease in many subjects.     

Symptoms and behavioral features induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in an old Java monkey [Macaca cynomolgus fascicularis (Raffles)]

The study concerns symptoms and behavioral characteristics induced by MPTP in a 20-year-old Macaca cynomolgus fascicularis, their evolution over 7 months, and the animal's response to 1-dopa treatment. The symptoms which the animal developed include those that have been described earlier in Macaca mulatta and Saimiri sciureus, i.e., rigidity, action tremor, postural tremor, postural flexion, hypokinesia, and bradykinesia. In addition, however, the animal developed a 3.8 Hz resting tremor which in humans is pathognomonic of Parkinson's disease, as well as cogwheeling, the glabellar tap sign, drooling, impaired ability to relax, and many other symptoms. Also unlike previously described MPTP monkeys, the animal's symptoms neither improved spontaneously, nor did they remain stable shortly after MPTP injection. Instead, symptoms steadily progressed to reach a severe status 2 months after MPTP, and further progression was apparent after another 5 months. Therapeutic responses to 1-dopa required accumulation of or kindling by the 100 mg unit doses that were spaced 4 hr apart, were often organized in time as ON episodes that alternated with OFF episodes, and were associated with dyskinesias and bizarre behavior. Of particular interest is that the animal showed kinesia paradoxa which, in humans, constitutes a feature that is unique to Parkinson's disease among the extrapyramidal disorders. In addition to available evidence, the present findings validate the syndrome induced by MPTP in monkey as an animal analogue of Parkinson's disease. Taxonomic category, age, and the occurrence of shock in response to MPTP are discussed as variables that may possibly co-determine the pathology which MPTP may induce in monkey.