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Expression of the myelin basic protein gene locus in neurons and oligodendrocytes in the human fetal central nervous system.

The myelin basic protein (MBP) gene locus is composed of two overlapping transcription units that share all of the MBP exons. One of these transcription units expresses the MBPs and the other expresses a family of proteins structurally related to the MBPs. This second transcription unit is called the Golli gene, and the entire complex is called the Golli-mbp gene. In this study, the expression of the Golli gene was examined in the human fetal central nervous system (CNS). By using reverse transcriptase-polymerase chain reaction cloning we have identified eight new members of the Golli gene family of transcripts expressed in the human CNS. Golli gene expression was examined by in situ hybridization and immunohistochemistry, and surprisingly, Golli products were found to be expressed in neurons as well as oligodendrocytes. Furthermore, the subcellular distribution of Golli immunoreactivity in fetal spinal cord interneurons shifted between the various laminae. Golli protein was localized within the nuclei of interneurons in the posterior horn, but was found in the cell bodies and processes of interneurons in the anterior horn. Within oligodendrocytes, Golli protein was detected in the cell bodies and processes, including processes which were wrapping axonal segments. Golli mRNA expression was also observed in neurons within the cerebral cortex between 18 and 20 weeks postconception, prior to myelination of this brain region. During this period, there was a striking developmental increase in the numbers and in the locations of neurons expressing Golli mRNAs within the cortical plate. The diverse distribution of Golli proteins within neurons and oligodendrocytes indicates that their function is quite different from that of the MBPs to which they are closely related.

Antibodies↗

Contemporary possibilities of medicamentous prevention of cataract.

The study is based upon the fact that aging processes inevitably affect all parts of the human body. These processes are often followed by pathological changes, whose basic cause may be some of the genetic factors or insufficient and inadequate nutrition, but they may also be intensified by the influence of adverse effects in the work place or ecologic factors. It is often impossible to completely avoid the impact of all these processes upon the human body, but the application of certain preventive measures and medicamentous therapy may diminish or slow them down. The results of the application of various medicaments with the purpose of slowing down the manifestation or progress of cataract have shown that such measures of the medicamentous prevention of cataract certainly have medical justification. It has also been found that the medicaments applied slowed down the development and progress of lens opacities and the occurrence of cataract to a higher or lesser degree, depending on the kind of preparation and its efficacy.

Adult↗

The chromatoid body: a germ-cell-specific RNA-processing centre.

The chromatoid body, a unique cloud-like structure of male germ cells, moves dynamically in the cytoplasm of haploid spermatids, but its function has remained elusive for decades. Recent findings indicate that microRNA and RNA-decay pathways converge to the chromatoid body. This highly specialized structure might function as an intracellular focal domain that organizes and controls RNA processing in male germ cells.

Animals↗

A perspective on sporadic inclusion-body myositis: the role of aging and inflammatory processes.

Sporadic inclusion-body myositis (sIBM) is an age-related condition manifested after midlife. This review points out salient features of sIBM that are shared with normal aging in muscle and with inflammatory changes in vascular atheromas and senile plaques of Alzheimer disease (AD). The amyloid precursor protein (APP) and derived Abeta peptides are found in both AD and sIBM. Because transgenic expression of human APP induces sIBM like changes, it is of potential interest that an inducer of APP, IL-1, increases during aging in mouse muscle. Because various subsets of the usual aging changes in aging brain, muscle, and vessels can be attenuated in rodents by caloric intake and possibly in humans by drugs with anti-inflammatory and anticoagulant activities, this study suggests that diet and inflammation may be useful experimental variations in exploring the pathogenesis of sIBM.

Aged↗

Evidence from cadavers suggestive of entrapment of fifth lumbar spinal nerves by lumbosacral ligaments.

Lumbosacral spines from 51 geriatric-age cadavers (25 men and 26 women) were examined both grossly and under the dissecting microscope for evidence of compression of fifth lumbar spinal nerves by their respective lumbosacral ligaments. These ligaments were found to extend from the transverse process and body of L5 to the ala of the sacrum in 97% of the specimens, and from the transverse process and body of L5 to the promontory of the sacrum in 3% of the specimens. Anterior primary rami of the fifth lumbar spinal nerve were observed to be compressed in 11% (11 of 102) of the specimens examined grossly and under the dissecting microscope. Histologic evidence of chronic compression, as suggested by perineurial and endoneurial fibrosis, peripheral thinning of myelin sheaths, or subjective evidence of a shift in fiber diameter to a population of smaller size fibers was found, deep to the lumbosacral ligament, in three of the 11 nerves judged to be compressed. The information derived is of interest to the clinician whose patient presents with L5 root signs and a myelogram, discogram, and computed tomographic scan which do not show any abnormality. The possibility of extraforaminal compression must be considered as a possible source of the clinical signs.

Aged↗

Medusa cells: cytostructure and cytochemistry of amoeboid eosinophils with pseudopod-like processes.

Eosinophils having one or more pseudopod-like processes of various lengths are observed in bone marrow, peripheral blood, sputum, nasal smears, and in other exfoliative cytology and tissue specimens after fixation and staining for histochemical study; they are called medusa cells. Although the conformations and lengths of the processes vary, they resemble protozoal pseudopodia. The form which first called our attention to these cells is a conical determinate projection that tapers to a fine tip, much like a protozoal axopod. A basal specialization in the form of a vesicle or thickening may be frequently observed where the process protrudes from, or appears attached to, the cell body. The processes of these eosinophil variants appear morphologically specialized to interact with other cellular elements of the blood and are occasionally seen in contact with, or engulfing, erythrocytes, platelets or other leukocytes. Two hydroperoxidases have been elucidated in eosinophils and medusa cells by virtue of different substrate specificities, subcellular localizations and inhibitor sensitivities. One of these hydroperoxidases is shown by 3,3'-diaminobenzidine, is cyanide resistant, and is never observed in granules or rods in the medusa cell processes; it is frequently polarized to the sites of contact of medusa cells with other cellular elements of the blood. The other hydroperoxidase is revealed by p-phenylenediamine-pyrocatechol, is sensitive to cyanide and is frequently observed in granules and rods in medusa cell processes as well as in a population of larger granules in the cell bodies; the granules in the processes appear to be precursors to the rods, which may be related to Charcot-Leyden crystals. The extrusion of medusa cell processes is facilitated by the divalent cations calcium and magnesium and is inhibited by anions which sequester them such as phosphate, EDTA, citrate and oxalate. Medusa cells have been observed in samples from both rodents and humans and can be very prominent when eosinophilia accompanies allergy, parasitosis and malignancy.

Asthma↗

Presynaptic alpha 2-adrenoceptors inhibit calcium influx in terminals of chicken sympathetic neurons and noradrenaline release evoked by nicotinic stimulation.

The changes of intracellular calcium concentration evoked by stimulation of nicotinic receptors and its modulation by alpha 2-adrenoceptors were investigated in chicken sympathetic neurons grown in culture. Stimulation of nicotinic receptors increased the intracellular calcium both in the area of cell bodies and processes. In normal extracellular calcium (1.3 mmol/l), the specific alpha 2-adrenoreceptor agonist UK 14,304 (10 mumol/l) diminished the response in cell bodies but not in processes. The same treatment in medium with reduced calcium (0.13 mmol/l) resulted in the decrease of the response evoked by nicotinic stimulation in the area of processes but not in the cell bodies. The effect of UK 14,304 on evoked noradrenaline release paralleled its influence on intracellular calcium in processes. These data indicate that nicotine stimulation-induced influx of calcium is inhibited by alpha 2-adrenoceptor stimulation both in cell bodies and in processes. It is concluded that the nicotinic stimulation-evoked release of noradrenaline is triggered by influx of calcium through alpha 2-adrenoreceptor sensitive as well as insensitive pathways.

Adrenergic alpha-2 Receptor Agonists↗

A trial of semiquantitative analysis of whole body bone scintigraphy in renal osteodystrophy.

Four color processed whole body bone scintigraphy with 99mTc-methylene diphosphonate was performed in six patients on maintenance hemodialysis, and the results of semiquantitative colorimetric analysis were compared with those of a normal group. The difference between the two (control and patient group) was statistically significant (P less than 0.01). Furthermore, the effect of 1 alpha-hydroxyvitamin D3 treatment on renal osteodystrophy was evaluated by this method. The results indicated that this method provides a useful method for assessing the response of renal osteodystrophy to treatment. Two representative cases of renal osteodystrophy are presented to illustrate the usefulness of this approach to semiquantitative whole body bone scanning.

Adult↗

Anomalous attachment of the transverse process to the vertebral body: an accessory finding in congenital absence of a lumbar pedicle.

A new case of congenital absence of a lumbar pedicle prompted a review of the English literature describing this rare defect. The majority of cases reported in detail were associated with anomalous attachment of a small ipsilateral transverse process directly to the posterior-lateral margin of the vertebral body. This sign is illustrated as a helpful accessory radiographic finding in congenital pedicle aplasia at a lumbar level.

Adult↗

Inhibition of adenylate cyclase in bovine ciliary process and rabbit iris ciliary body to alpha 2-adrenergic agonists.

Alpha 2-adrenergic inhibition of adenylate cyclase in bovine ciliary processes and rabbit iris ciliary body (ICB) was studied. With bovine ciliary process membrane, it was found that cAMP production in the presence of 1 microM isoproterenol was increased with increasing NaCl concentrations from 0 to 200 mM. Clonidine, an alpha 2-adrenergic agonist, produced a NaCl concentration-dependent inhibition of cAMP production in the presence of isoproterenol with a maximum inhibition at 200 mM NaCl (P less than 0.05). NaCl concentrations had no effect on basal adenylate cyclase activities and activity in the presence of clonidine alone. The alpha 2-adrenergic agonists, lofexidine, clonidine and p-amino-clonidine were tested for their ability to inhibit isoproterenol-stimulated adenylate cyclase in bovine ciliary process membrane in the presence of 200 mM NaCl. Their dose-response curves showed that they had similar IC50's but the maximum inhibition differed among these agonists. Clonidine was found to be a partial agonists producing 55% of the inhibition obtained with lofexidine. The specificity of inhibition of isoproterenol-stimulated adenylate cyclase by alpha 2-agonists and blockade by pertussis toxin was examined by adenine labelling in rabbit ICB. The results demonstrate that alpha 2-adrenergic receptors exert specific inhibitory effects on adenylate cyclase activity in rabbit ICB, which are mediated by an inhibition guanine nucleotide regulatory protein, Gi.

Adenine↗

Cultured oligodendrocytes mimic in vivo phenotypic characteristics: cell shape, expression of myelin-specific antigens, and membrane production.

Primary cultures of neonatal mouse cerebra were maintained for up to 4 weeks in the absence of neurons. Oligodendrocytes in these cultures pass through a sequence of cytoarchitectural change and antigen expression which mimics the differentiation of oligodendrocytes in vivo. The cell bodies and processes of oligodendrocytes first express the myelin-specific antigen galactocerebroside (GC) by 2 days in vitro. Myelin basic protein (MBP) appears several days later. The majority of oligodendrocytes then proceed to elaborate large sheets of membranous material from the tips and lengths of cell processes. These membranous sheets, which contain GC and MBP, are reminiscent of unwrapped myelin profiles in vivo. As with the cell bodies and processes, GC is inserted into the sheets several days before MBP. Our results establish that oligodendrocytes cultured without neurons are able to produce extensive membranes containing myelin-specific antigens. They also suggest that oligodendrocyte shape and membrane production are, in part, regulated from within the oligodendrocyte itself.

Animals↗

Renal physiology series: part 7 of 8: renal acidification.

Maintenance of a normal body pH is essential to the efficient functioning of many physiologic processes. The body has a number of mechanisms for preventing fluctuations in body pH. Some of these are designed to prevent minute-to-minute pH fluctuations over the course of the day, and others are designed to maintain pH balance from day to day. The kidney plays a key role in both processes. The renal process of bicarbonate reclamation prevents the loss of bicarbonate in the urine, and thus, maintains plasma levels of one substrate that is instrumental to preventing minute-to-minute pH fluctuations. The other renal process, bicarbonate regeneration, replenishes the body's supply of bicarbonate, and thus, maintains pH balance on a day-to-day basis. This article will discuss basic principles of acid-base physiology, the mechanisms designed to prevent fluctuations in body pH, and the renal processes instrumental in maintaining a homeostatic pH environment.

Acid-Base Equilibrium↗

Renal regulation of acid-base balance.

Because maintaining a normal body pH is essential to the efficient functioning of many physiologic processes, the body has a number of mechanisms that prevent pH fluctuations. Some of these prevent minute-to-minute pH fluctuations over the course of the day, whereas others maintain pH balance from day to day. The kidney plays a key role in both processes. The renal process of bicarbonate reclamation prevents the loss of bicarbonate in the urine and, thus, maintains plasma levels of one substrate that is instrumental to preventing minute-to-minute pH fluctuations. The other renal process, bicarbonate regeneration, replenishes the body's supply of bicarbonate and, thus, maintains pH balance on a day-to-day basis. This article will discuss basic principles of acid-base physiology, the mechanisms that prevent fluctuations in body pH, and the renal processes involved in maintaining a homeostatic pH environment.

Acid-Base Equilibrium↗

Lipase inhibition and hormonal status, body composition and gastrointestinal processing of a liquid high-fat mixed meal in moderately obese subjects.

The effect of Orlistat, a lipase inhibitor used in the treatment of obesity was studied on gastrointestinal transit time, on body composition and on hormones known to be influenced by the degree of hydrolysis of nutritional triglycerides or by reduced nutrient intake and absorption. After a placebo run-in period 14 patients were randomized to a 12-week treatment period on Orlistat 360 mg per day (mean body weight 93.1 +/- 9.8 kg) or placebo (mean body weight 90.7 +/- 10.5 kg). At randomization and after 12 weeks body weight, body composition, thyroid hormones, catecholamines, insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were measured. During 4 hours after consumption of a liquid fat-rich mixed meal containing study medication, 15 g lactulose and 25 g xylose, blood levels of glucose, insulin, c-peptide, glucagon, triglycerides, free fatty acids, cholecystokinin, pancreatic polypeptide and xylose and expiration air levels of hydrogen were measured. Weight loss was 4.2 +/- 3.5 kg in the Orlistat group versus 3.0 +/- 1.9 kg in the placebo group. Fat mass decreased to an equal degree, whereas lean body mass remained stable. No differences were found for thyroid hormones, catecholamines, IGF-I and IGFBP-3 levels. By comparing the areas under the curve (AUC) and the peak levels at randomization (acute effects) of insulin and c-peptide a tendency was found to be increased in the Orlistat group, whereas those of xylose were increased significantly, suggesting faster gastric emptying after Orlistat. No differences were found in the other parameters. By comparing the changes in responses (longer term effects) no significant differences were found. In conclusion, the presence in the gut of undigested and unabsorbed fat does not seem to have a relevant influence on hormonal status and body composition in a small group of moderately obese patients.

Body Composition↗

Distribution of somatostatin-immunoreactive cell bodies and fibers in the neocortex of Macaca fuscata.

The distribution of somatostatin-immunoreactive cell bodies and processes was studied in the cerebral cortex of the macaque monkey (Macaca fuscata), by applying an immunohistochemical technique with a monoclonal antibody raised against somatostatin tetradecapeptide. Many somatostatin-immunoreactive cell bodies and processes were observed in all regions of the cerebral cortex, i.e., frontal, parietal, temporal, insular, occipital, and cingulate cortices, and also in the underlying white matter. Three types of somatostatin-containing cell bodies were distinguished in the cerebral cortex. These cell bodies were distributed in layers II to VI of the cortex, and also in the underlying white matter. There were dense deposits of somatostatin-containing granular structure in layers I and II, and many somatostatin-containing processes in layers IV and V. The present observations demonstrate that in the primate neocortex somatostatin 14-containing neuronal systems are as highly developed as other prosomatostatin-derived peptides but differ from the latter systems in terms of cell morphology and fiber distribution.

Animals↗

Guidance of neuritic growth in the transverse plane of embryonic mouse spinal cord.

The development of cytoarchitecture in the lumbar spinal cord of mouse embryo between embryonic day 13 (E13) and E15 was studied by scanning and transmission electron microscopy. A pattern of two perpendicularly oriented sets of cellular elements was found in the intermediate zone at both E13 and E14. One set consisted of radially oriented processes that often originated from cell bodies in the ventricular zone. The second set consisted of cell bodies and processes that were oriented predominantly parallel to the neural tube margin and in the transverse plane. This set was termed circumferential elements and included most of the immature neurons. At E13, the circumferentially oriented cells were arranged into rostrocaudally compressed sheets or layers that were partially segregated one from another by flattened bundles of radially oriented processes. This pattern of orthogonally arranged circumferential and radial elements remained evident through E14 when the profuse growth of cellular processes began of obscure the identity of individual cells seen on the scanned surface. The exposed intermediate zone surface at E14 and E15 often has relatively flat transverse areas separated by ledges of broken tissues, indicating that most neurites grow in the transverse plane. These observations indicate that the sequential patterned development of an organized morphological substratum is an important factor in orienting neurite growth.

Animals↗

Proteasome inhibitors protect against degeneration of nigral dopaminergic neurons in hemiparkinsonian rats.

Parkinson's disease is characterized by dopaminergic neuronal death and the presence of Lewy bodies in the substantia nigra pars compacta (SNpc). alpha-Synuclein and ubiquitin are components of Lewy bodies, but the process of Lewy body formation and the relationship between inclusion formation and dopaminergic neuronal death have not been resolved. In this study, unilateral intranigral microinjection of 6-hydroxydopamine caused a significant loss of tyrosine hydroxylase-immunopositive neurons in both the substantia nigra and striatum and apomorphine-induced contralateral rotation. The co-administration of proteasome inhibitors, such as lactacystin or carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG-132), significantly prevented both dopaminergic neurodegeneration and apomorphine-induced rotational asymmetry. Proteasome inhibitors markedly formed intracellular protein inclusions labeled by thioflavin-S in the SNpc. Inclusion-like immunoreactivities for alpha-synuclein and ubiquitin were detected after 4 weeks. These results suggest that proteasome plays an important role in both the early phase of dopaminergic neuronal death and inclusion body formation.

Animals↗