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Biomedical subjects

J Sage

Publications and source records attributed to J Sage.

At least 37 records · Page 2Linked to original sources

The Sycp1 loci of the mouse genome: successive retropositions of a meiotic gene during the recent evolution of the genus.

The murine Sycp1 gene is expressed at the early stages of meiosis. We show that it is composed of a number of small exons and localized on mouse chromosome 3. In the laboratory strains, two retrogenes were also identified. The first one (Sycp1-ps1), on chromosome 7, has accumulated point mutations and deletions and is not transcribed. A second retrogene (Sycp1-ps2), on chromosome 8, is inserted within the continuity of a moderately repeated element, in an intron of another gene (Cad11). The two retroposition events can be dated to distinct periods in the evolution of the Muridae. Sycp1-ps2 has kept features indicative of a relatively recent origin, namely a nearly intact coding region, a poly(A) tail, and 14-bp terminal repeats. Its recent origin was confirmed by the fact that it is found in all the laboratory strains of mice, but neither in a recent isolate from Mus musculus domesticus wild stocks nor in the closely related subspecies M. musculus musculus, M. m. molossinus, M. m. castaneus, and M. m. bactrianus. Appearance of the more ancient Sycp1-ps1 retrogene is concomitant with the radiation of the genus. It is present in various Mus species (M. spretus, M. spicilegus, M. macedonicus, and M. cookii), but neither in the rat nor in the more closely related Pyromis genus. Transposition of retrotranscripts during meiosis and their hereditary establishment thus appear to occur relatively frequently. They may, therefore, play a significant role in the evolutionary process.

Animals↗

Stage-specific signals in germ line differentiation: control of Sertoli cell phagocytic activity by spermatogenic cells.

Differentiation of male germ cells requires a continuous cross-talk with their somatic support, the Sertoli cell. An in vitro model of Sertoli cells was recently provided by established cell lines which maintain Sertoli-specific characteristics, among which is a regulated phagocytic capacity. In vivo, Sertoli cells take up the residual cytoplasm expelled from the maturing sperm, a process restricted to a limited period of germinal maturation, and they also eliminate abnormally differentiated germ cells in case of hormonal deficiency. Cells of the Sertoli line efficiently take up latex beads, as well as dead cells in the cultures. A semiquantitative assay of phagocytosis was developed, based on the uptake of fluorescent latex beads. 15P-1 cultures were found to contain a minor fraction of active phagocytes. After addition of a defined fraction of germ cells, however, all the cells internalized beads as efficiently as macrophages. The inducing cell was identified as the pachytene spermatocyte, a cell type which, in vivo, is associated with Sertoli cells when they express their phagocytic potential. These inducing meiotic cells were not internalized themselves. Rather, they interacted with Sertoli cells via a surface signal that was resistant to formaldehyde fixation. The whole induction process does not involve changes in Sertoli gene expression, since it occurs even in the presence of high doses of cycloheximide. After the required initial contact, further maintenance of the activity was dependent on factor(s) secreted in the medium of the activated culture. Phagocytosis was, on the other hand, abrogated in the presence of factor(s) secreted by a distinct fraction of germ cells, enriched in the late stages (second division) of meiosis.

Animals↗

Complete sequencing of the murine USF gene and comparison of its genomic organization to that of mFIP/USF2.

USF is a transcription factor able to stimulate promoter activity upon binding to an upstream sequence identical to that recognized by the protooncogene Myc. However, despite extensive biochemical characterization, nothing is known concerning its physiological function. A USF-related protein able to interact with Fos and known as FIP/USF2 has been reported. Its genomic structure in mouse has been recently characterized. We present here the cloning and characterization of the murine USF gene. It consists of 10 exons, the first of which is noncoding, and the gene spans 8 kb of DNA. We show that the murine USF protein is almost identical to its human counterpart, but that an intron not conserved between human and murine USF genes curiously has been conserved between human USF and murine FIP/USF2. Otherwise, the splicing pattern of murine USF and FIP/USF2 is exactly conserved. We also demonstrate that the murine USF promoter is located more than 2.5 kb upstream of the first coding ATG, in a region displaying divergent promoter activity. Finally, we show that an Mx1-related sequence is present less than 3 kb downstream of the murine USF gene, in a tail-to-tail position. Taken together, these data indicate that the murine USF gene is very similar to the murine FIP/USF2 gene and is potentially bracketed by two other transcription units on the other DNA strand.

Amino Acid Sequence↗

An electrical impedance tomography microscope.

A circular array of 16 electrodes has been constructed for use as an electrical impedance tomography (EIT) microscope. The electrodes were made from 60 microns diameter gold wires anchored to a printed circuit board. The internal diameter of the array was 0.9 mm giving a theoretical spatial resolution of about 100 microns. For EIT imaging, the array was connected to an imaging system operating at 82 kHz. Static images of conducting and insulating filaments (cooper wire and human hair) in saline solution were obtained as well as dynamic imaging sequences of glass microspheres migrating through the array. The interelectrode impedance was typically 5 k omega and the transimpedances ranged from 14 to 210 omega.

Electric Impedance↗

cDNA sequence of the murine synaptonemal complex protein 1 (SCP1).

We isolated and sequenced cDNAs for the murine synaptonemal complex protein 1 (SCP1). The whole cDNA sequence displays respectively 93% and 90% identity with the previously reported rat and hamster cDNAs. We show, however, that the encoded amino acid sequence extends for an additional stretch of 51 residues at its amino-terminal end.

Amino Acid Sequence↗

Peri- and postoperative magnetic resonance imaging localization of pallidotomy.

Postoperative magnetic resonance imaging (MRI) of basal ganglia functional lesions illustrates the accuracy of preoperative target localization. The technique of perioperative MRI and CT localization for pallidotomy will be discussed and correlated with the center of the lesion on postoperative standard MRI as well as three-dimensional (3-D) volume acquisition of image. Using a 1.5-tesla Signa system, a conventional acquisition of 128-slice, 256 x 256 matrix spoiled grass (SPGR) images were used for 3-D reformation. This allowed approximately 1 x 1 x 2 mm resolution over a 24-cm field of view in a T-1-weighted image. The display affords a volumetric analysis of the anatomic location and relation of the post-ventral pallidotomy to adjacent structures. Accuracy lesion placement based on perioperative MR coordinates and revealed on postoperative images is confirmed. The volume of the lesion as well as its location are factors that affect clinical outcome.

Basal Ganglia↗

Transmeiotic differentiation of male germ cells in culture.

A cell culture system that supports the differentiation of male germ cells through meiosis is described. It takes advantage of the properties of a cell line, 15P-1, established from testicular cells of transgenic mice that express the large T protein of polyoma virus in the seminiferous epithelium. This line exhibits features characteristics of Sertoli cells, including transcription of the Wilms' tumor (WT1) and Steel genes. Cells of the 15P-1 type support the meiotic and postmeiotic differentiation in cocultures of diploid premeiotic germ cells into haploid spermatids expressing the protamine (Prm-1) gene. When cocultured with 15P-1 cells, testicular cells explanted from immature 9-day-old animals, before the onset of the first meiosis, generated tetrads of haploid cells with the morphology of round spermatids and initiated protamine transcription.

Animals↗

Mood changes and "on-off" phenomena in Parkinson's disease.

Ten patients with idiopathic Parkinson's disease and motor fluctuations were rated for mood changes during discrete "off," "on," and "on with dyskinesia" periods. The Profile of Mood States and visual analogue scales were used. Significant changes in mood and anxiety were found to parallel changes in motor fluctuations. One patient rated his moods as consistently improving from the "off" state to the "on" state and finally to the "on with dyskinesia" state, a finding that is consistent with concomitant central dopaminergic changes. All other patients showed moods that improved significantly from the "off" state to the "on" state but then worsened significantly in the "on with dyskinesia" state, a finding that is consistent with the fact that patients feel worse when impaired by dyskinesias. It is suggested that these results argue for multiple etiologies of depression in Parkinson's disease. The literature on dopamine and depression in Parkinson's disease is briefly reviewed and the opportunity provided by "on-off" phenomena to study the effect of dopamine on mood changes is discussed.

Affect↗

Low leukocyte glutamate dehydrogenase activity does not correlate with a particular type of multiple system atrophy.

Leucocyte glutamate dehydrogenase (GDH) activity was measured in 26 normal control subjects, 20 patients with multiple system atrophy presenting features of either olivopontocerebellar atrophy or striatonigral degeneration and in a heterogenous group of 15 patients with spinocerebellar degenerations. A broad range of GDH activity was found in all three groups. Low activity failed to correlate with a specific clinical entity. Patients followed to post-mortem examination to date have demonstrated histological features of at least three distinct morbid entities. It is concluded, contrary to earlier reports including the authors', that low leukocyte GDH activity does not identify a particular type of multiple system atrophy.

Adult↗

Neurophysiologic study of olivopontocerebellar atrophy with or without glutamate dehydrogenase deficiency.

By neurophysiologic investigations, we evaluated 20 patients with olivopontocerebellar atrophy (OPCA), comprising 8 with glutamate dehydrogenase (GDH) deficiency and 12 with normal GDH activity. We found sensorimotor, predominantly sensory axonal neuropathy distally in the legs, and peripheral auditory nerve dysfunction (prolonged wave I but normal interpeak latencies in brainstem auditory evoked response) in GDH-deficient patients. These findings seem distinctive enough to serve as the electrophysiologic marker for diagnosis and monitoring of treatment and progression of the disease. The pattern-reversal visual and median nerve somatosensory evoked responses did not differ among the patients and controls.

Aged↗