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Biomedical subjects

E C Jacobs

Publications and source records attributed to E C Jacobs.

At least 19 recordsLinked to original sources

Identification of a new exon in the myelin proteolipid protein gene encoding novel protein isoforms that are restricted to the somata of oligodendrocytes and neurons.

The myelin proteolipid protein (PLP) gene (i.e., the PLP/DM20 gene) has been of some interest because of its role in certain human demyelinating diseases, such as Pelizaeus-Merzbacher disease. A substantial amount of evidence, including neuronal pathology in knock-out and transgenic animals, suggests the gene also has functions unrelated to myelin structure, but the products of the gene responsible for these putative functions have not yet been identified. Here we report the identification of a new exon of the PLP/DM20 gene and at least two new products of the gene that contain this exon. The new exon, located between exons 1 and 2, is spliced into PLP and DM20 mRNAs creating a new translation initiation site that generates PLP and DM20 proteins with a 12 amino acid leader sequence. This leader sequence appears to target these proteins to a different cellular compartment within the cell bodies of oligodendrocytes and away from the myelin membranes. Furthermore, these new products are also expressed in a number of neuronal populations within the postnatal mouse brain, including the cerebellum, hippocampus, and olfactory system. We term these products somal-restricted PLP and DM20 proteins to distinguish them from the classic PLP and DM20 proteolipids. They represent putative candidates for some of the nonmyelin-related functions of the PLP/DM20 gene.

Aging↗

Developmental regulation of the distribution of aromatase- and estrogen-receptor- mRNA-expressing cells in the zebra finch brain.

Strong evidence exists for the masculinizing effects of estrogen on the neural network that controls song learning and behavior in zebra finches. However, the mechanisms by which estrogen acts to influence the development of this circuitry are not well understood. In this study, we used in situ hybridization to detect the distribution of cells expressing mRNAs for AROM and ERalpha at postnatal days 5-25 (P5-25). Our findings revealed developmental regulation of both mRNAs in the neostriatum, archistriatum, hippocampus, diencephalon and midbrain. Within the vocal control circuitry, cells expressing ERalpha mRNA were found in the medial HVC (P10-25), archistriatum lateral to the RA (Ad; P25), in the ICo (P5-25), and along the fiber tract containing efferents from the RA. High levels of AROM mRNA were found in the neostriatum, including both the lateral and mMAN and along their projections to the RA and HVC, respectively, (P5-25), in the archistriatum (P18-25) and around RA (P18). Codistribution of the two mRNAs occurred along the border of the HVC suggesting that in this region, local synthesis of estrogen may be acting through its nuclear receptor to regulate gene transcription. Taken together, our findings show that the neural circuitry controlling song may be exposed to the effects of estrogen during early postnatal development. However, in most of the song control regions, these mRNAs were not expressed together either temporally or spatially, indicating that AROM may have a role in the development of the song system independent of ERalpha.

Animals↗

Zebra finch estrogen receptor cDNA: cloning and mRNA expression.

In zebra finches, estrogen is a potent hormone that masculinizes the neural circuitry controlling song during development and activates song in adulthood. However, previous studies have reported conflicting patterns of estrogen receptor (ER) expression in the song control regions. To obtain additional information about the distribution of ER in the zebra finch brain, a cDNA encoding an estrogen receptor was isolated from a zebra finch hypothalamic-preoptic area cDNA library. The 2792 bp insert contains a 1764 bp open reading frame with 5' and 3' untranslated regions of 132 bp and 896 bp, respectively. The deduced polypeptide is 589 amino acids in length and is highly homologous to the estrogen receptors of chicken (97%), rat (79%), mouse (79%), human (78%), Xenopus laevis (76%) and trout (49%). Northern blot analysis revealed three ER mRNAs expressed differentially in ovary, oviduct and telencephalon. The smallest transcript, 4.1 kb, was expressed in all three tissues, whereas larger mRNAs were expressed in ovary (7.6 kb) and oviduct (8.1 kb). In situ hybridization histochemistry revealed strong labelling in the infundibular region of the hypothalamus, preoptic area, and medial caudal neostriatum. Few or no labelled cells were found in the song control nuclei (HVC, RA, MAN or Area X). These results are consistent with previous studies that have shown ER protein and binding in hypothalamic and preoptic area and a lack of ER in most regions that control song production.

Amino Acid Sequence↗

Sexual differentiation of the brain in songbirds.

The brain regions that control song in zebra finches are much larger in males, who sing, than in females, who do not. Two major theories have been proposed to explain sexual differentiation of the neural song circuit. The 'mammalian' theory suggests that sex steroid secretions of the tests cause masculine development in males. The 'avian' theory suggests that ovarian secretions induce feminine patterns of development in females. Although experimental evidence provides some support for the mammalian theory, neither theory comfortably predicts the outcomes of experiments that bear on the mechanisms of sexual differentiation. In particular, it has been relatively difficult to block sex steroid synthesis and action in genetic males in a way that prevents masculine neural differentiation. Moreover, genetic females that possess large amounts of testicular tissue can have a feminine neural song circuit, suggesting that testicular secretions are not solely responsible for the masculine patterns of differentiation. The results indicate that new theories are needed to explain sexual differentiation of the song system.

Animals↗

Lack of a synergistic effect between estradiol and dihydrotestosterone in the masculinization of the zebra finch song system.

Previous studies have suggested that both major active metabolites of testosterone, estradiol (E2) and dihydrotestosterone (DHT), are needed for complete masculinization of the brain regions that control song in passerine birds. However, DHT treatment of hatchling female zebra finches has only small masculinizing effects on the song system. To assess whether E2 and DHT have a synergistic effect on the masculinization of the zebra finch song system, female zebra finches were given Silastic implants of E2 on the day of hatching (day 1) either without any additional hormone treatment or in combination with DHT on days 1, 14, or 70. At 105 to 110 days of age, we measured the volumes of Area X, higher vocal center (HVC), robust nucleus of the archistriatum (RA), soma sizes in HVC, RA, and the lateral magnocellular nucleus of the neostriatum (IMAN), and neuron density and number in RA. E2 masculinized all of the measures in the song system with the exception of the number of neurons in RA. DHT did not synergize with E2 to produce any additional masculinization of the attributes measured. These data demonstrate that the combination of E2 and DHT did not result in the complete masculinization of the song control nuclei and argue against the importance of androgen in sexual differentiation of the song system.

Analysis of Variance↗

EView--a workstation-based viewer for intensive clinical electroencephalography.

We describe a workstation-based EEG viewer that satisfies the requirements for high-volume clinical EEG review. It currently supports two 24-h four-bed epilepsy monitoring units and a network of routine, intraoperative, and intensive care monitors, providing paperless review of over 5000 pages/day by a staff of clinical neurophysiologists. The design takes advantage of the development environment, processing and graphics resources, and networking capabilities of high-performance UNIX workstations. The user interface and operational infrastructure have been tailored to the demands of clinical neurophysiologists requiring rapid access to large volumes of EEG waveform data in a large clinical neurophysiology laboratory. This paper describes the functional requirements, system architecture, and implementation details of the current system.

Computer Systems↗

Data interchange for clinical neurophysiology.

Clinical Neurophysiology is rapidly moving towards complete dependence on digital instrumentation and computer-based systems. ASTM E 1467-92 "Standard Specification for Transferring Digital Neurophysiological Data Between Independent Computer Systems" was developed to allow exchange of multichannel electrophysiological waveforms, embedded textual annotations, results of mathematical processing, and clinical interpretive reports between various instruments and systems. This will permit integration of the neurophysiology laboratory interaction with hospital and clinic informations systems, and sharing of data between institutions for clinical or research purposes.

Computer Systems↗

A data interchange standard for clinical neurophysiology.

A Standard Specification for Transferring Digital Neurophysiological Data Between Independent Computer Systems (Designation E 1467-92) has been developed. The specification defines a common representation of all of the data associated with a complete clinical study, including digitized neurophysiological waveforms, textual annotations and interpretive reports. Patterned after existing, related healthcare data interchange standards, it will facilitate data interchange between neurophysiological instruments, computer systems within the neurophysiology laboratory, other information systems in the hospital, and outside healthcare facilities or research laboratories.

Computer Communication Networks↗

Renal dysgenesis and cystic disease of the kidney: a report of the Committee on Terminology, Nomenclature and Classification, Section on Urology, American Academy of Pediatrics.

We believe that the confusion regarding abnormal renal development could be reduced by more precise terminology. Therefore, we suggest precise definitions for dysgenesis, hypoplasia, dysplasia, hypodysplasia, aplasia and agenesis of the kidney. We suggest the term reflux nephropathy be a generic label for any instance of abnormal renal morphology (gross or microscopic) associated with vesicoureteral reflux. Hypoplasia and hypodysplasia can be subclassified on the basis of associated urological criteria. There have been many previous attempts to classify cystic disease of the kidney but none has been accepted collectively by pathologists, urologists, nephrologists and radiologists. On the basis of known patterns of inheritance, a classification is outlined in which renal cystic disease is divided into 2 major groups: genetic and nongenetic. Each entity is discussed.

Classification↗

Fluorescent staining of fungal nuclei with a benzimidazol derivative.

A direct staining procedure is described for fluorescence microscopy of fungal nuclei, chromosomes and mitochondria. The fluorochrome is a benzimidazol derivative (33258 Hoechst) known to bind selectively to deoxyribonucleic acid at neutral pH. The advantages of 33258 Hoechst relative to Feulgen compounds used previously to stain these structures include a greater intensity of fluorescence, the absence of fading or rapid quenching of the fluorescence, and the omission of acid hydrolysis from the procedure for removal of ribonucleic acid. 33258 Hoechst has been evaluated as a nuclear stain with a yeast (Saccharomyces cerevisiae) and a filamentous fungus (Agaricus bisporus) and appears to penetrate easily vegetative cells and spores of both fungi.

Basidiomycota↗