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Biomedical subjects

C A Turner

Publications and source records attributed to C A Turner.

18 recordsLinked to original sources

Screen detected sclerosing lymphocytic lobulitis and amyloid of the breast in the same patient--a possible causal link.

Sclerosing lymphocytic lobulitis (SLL) and amyloidosis of the breast are both rare. We report the case of a 59 year old woman who presented with suspicious microcalcifications on routine screening mammography. Wire-guided excision biopsy showed features typical of SLL but also localised amyloid deposits within the specimen. Amyloidosis and SLL may have similar immunological causes. This patient represents the first documented association of these two disorders.

Amyloidosis↗

Spontaneous stereotypy in an animal model of Down syndrome: Ts65Dn mice.

Stereotyped behaviors (e.g., body rocking) occur at high rates in individuals with mental retardation (e.g., Down syndrome). To determine if spontaneous stereotypy occurs in a murine model of Down syndrome, the home cage behavior of Ts65Dn and control mice was monitored during the dark cycle. Motor activity was further assessed in novel automated test chambers, with acoustic startle and rotor rod paradigms providing additional environmental challenges. Spontaneous stereotypy (repetitive jumping and cage top twirling) was observed in the home cage in approximately half of the Ts65Dn mice, compared with approximately 10% of diploid controls. Repetitive jumping was observed exclusively in the Ts65Dn mice. In the open field, although no differences were found between Ts65Dn and control mice, stereotypic Ts65Dn mice exhibited significantly less locomotor activity and rearing relative to control and nonstereotypic Ts65Dn mice. Ts65Dn mice attained significantly lower rotor rod speeds but did not differ from controls in the amplitude of the acoustic startle response. These environmental challenges did not increase stereotypy over home cage rates but induced stereotypy in two additional animals. The Ts65Dn model may aid in identifying genes associated with the development and expression of stereotypy.

Acoustic Stimulation↗

Proteinuria and perinatal lethality in mice lacking NEPH1, a novel protein with homology to NEPHRIN.

A high-throughput, retrovirus-mediated mutagenesis method based on gene trapping in embryonic stem cells was used to identify a novel mouse gene. The human ortholog encodes a transmembrane protein containing five extracellular immunoglobulin-like domains that is structurally related to human NEPHRIN, a protein associated with congenital nephrotic syndrome. Northern analysis revealed wide expression in humans and mice, with highest expression in kidney. Based on similarity to NEPHRIN and abundant expression in kidney, this protein was designated NEPH1 and embryonic stem cells containing the retroviral insertion in the Neph1 locus were used to generate mutant mice. Analysis of kidney RNA from Neph1(-/-) mice showed that the retroviral insertion disrupted expression of Neph1 transcripts. Neph1(-/-) pups were represented at the expected normal Mendelian ratios at 1 to 3 days of age but at only 10% of the expected frequency at 10 to 12 days after birth, suggesting an early postnatal lethality. The Neph1(-/-) animals that survived beyond the first week of life were sickly and small but without edema, and all died between 3 and 8 weeks of age. Proteinuria ranging from 300 to 2,000 mg/dl was present in all Neph1(-/-) mice. Electron microscopy demonstrated NEPH1 expression in glomerular podocytes and revealed effacement of podocyte foot processes in Neph1(-/-) mice. These findings suggest that NEPH1, like NEPHRIN, may play an important role in maintaining the structure of the filtration barrier that prevents proteins from freely entering the glomerular urinary space.

Amino Acid Sequence↗

Role of the His273 located in the sixth transmembrane domain of the angiotensin II receptor subtype AT2 in ligand-receptor interaction.

Angiotensin II receptor subtypes AT1 and AT2 are proteins with seven transmembrane domain (TMD) topology and share 34% homology. It was shown that His256, located in the sixth TMD of the AT1 receptor, is needed for the agonist activation by the Phe8 side chain of angiotensin II, although replacing this residue with arginine or glutamine did not significantly alter the affinity binding of the receptor. We hypothesized that the His273 located in the sixth transmembrane domain of the AT2 receptor may play a similar role in the functions of the AT2 receptor, although this residue was not identified as a conserved residue in the initial homology comparisions. Therefore, we replaced His273 of the AT2 receptor with arginine or glutamine and analyzed the ligand-binding properties of the mutant receptors using Xenopus oocytes as an expression system. Our results suggested that the AT2 receptor mutants His273Arg and His273 Glu have lost their affinity to [125I-Sar1-Ile8]Ang II, a peptidic ligand that binds both the AT1 and AT2 receptors and to 125I-CGP42112A, a peptidic ligand that binds specifically to the AT2 receptor. Thus, His273 located in the sixth TMD of the AT2 receptor seems to play an important role in determining the binding properties of this receptor. Moreover, these results along with our previous observation that the Lys215 located in the 5th TMD of the AT2 receptor is essential for its high affinity binding to [125I-Sar1-Ile8]Ang II indicate that key amino acids located in the 5th and 6th TMDs of the AT2 receptor are needed for high affinity binding of the AT2 to its ligands.

Amino Acid Substitution↗

Spike detection II: automatic, perception-based detection and clustering.

OBJECTIVES: We developed perception-based spike detection and clustering algorithms. METHODS: The detection algorithm employs a novel, multiple monotonic neural network (MMNN). It is tested on two short-duration EEG databases containing 2400 spikes from 50 epilepsy patients and 10 control subjects. Previous studies are compared for database difficulty and reliability and algorithm accuracy. Automatic grouping of spikes via hierarchical clustering (using topology and morphology) is visually compared with hand marked grouping on a single record. RESULTS: The MMNN algorithm is found to operate close to the ability of a human expert while alleviating problems related to overtraining. The hierarchical and hand marked spike groupings are found to be strikingly similar. CONCLUSIONS: An automatic detection algorithm need not be as accurate as a human expert to be clinically useful. A user interface that allows the neurologist to quickly delete artifacts and determine whether there are multiple spike generators is sufficient.

Adolescent↗

FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation.

The hematopoietic transcription factor GATA-1 is essential for development of the erythroid and megakaryocytic lineages. Using the conserved zinc finger DNA-binding domain of GATA-1 in the yeast two-hybrid system, we have identified a novel, multitype zinc finger protein, Friend of GATA-1 (FOG), which binds GATA-1 but not a functionally inactive mutant lacking the amino (N) finger. FOG is coexpressed with GATA-1 during embryonic development and in erythroid and megakaryocytic cells. Furthermore, FOG and GATA-1 synergistically activate transcription from a hematopoietic-specific regulatory region and cooperate during both erythroid and megakaryocytic cell differentiation. These findings indicate that FOG acts as a cofactor for GATA-1 and provide a paradigm for the regulation of cell type-specific gene expression by GATA transcription factors.

3T3 Cells↗

Intraoperative monitoring of motor evoked potentials: a review of 116 cases.

We reviewed the results of motor evoked potential (MEP) and somatosensory evoked potential (SEP) monitoring during 116 operations on the spine or spinal cord. We monitored MEPs by electrically stimulating the spinal cord and recording compound muscle action potentials from lower extremity muscles and monitored SEPs by stimulating posterior tibial or peroneal nerves and recording both cortical and subcortical evoked potentials. We maintained anesthesia with an N2O/O2/opioid technique supplemented with a halogenated inhalational agent and maintained partial neuromuscular blockade using a vecuronium infusion. Both MEPs and SEPs could be recorded in 99 cases (85%). Neither MEPs nor SEPs were recorded in eight patients, all of whom had preexisting severe myelopathies. Only SEPs could be recorded in two patients, and only MEPs were obtained in seven cases. Deterioration of evoked potentials occurred during nine operations (8%). In eight cases, both SEPs and MEPs deteriorated; in one case, only MEPs deteriorated. In four cases, the changes in the monitored signals led to major alterations in the surgery. We believe that optimal monitoring during spinal surgery requires recording both SEPs and MEPs. This provides independent verification of spinal cord integrity using two parallel but independent systems, and also allows detection of the occasional insults that selectively affect either motor or sensory systems.

Evoked Potentials, Motor↗

Propagation patterns of temporal spikes.

In standard EEG recordings, spikes appear as single events characterized mainly by the scalp location of the their peak voltage. The signal-to-noise ratio of raw EEG is usually too high to permit more detailed analysis. We used spike averaging to improve the resolution of interictal spikes in 40 patients with temporal lobe epilepsy. Spikes were identified visually in raw, digitally stored EEG. When multiple spike types were present in a patient, they were grouped separately. Spikes were synchronized for averaging by aligning their negative peaks in a designated channel. Sixteen patients demonstrated spike propagation from anterior temporal to posterior temporal electrode locations. Thirty-six patients demonstrated spread of spikes from anterior temporal to fronto-polar electrode sites. While anterior temporal and fronto-polar spikes were often synchronous, fronto-polar spikes followed anterior temporal discharges in 25% of cases and preceded them in 13%. Spike averaging revealed propagation patterns not apparent on visual inspection of raw EEG. We speculate that these patterns may reflect inherent physiological properties of temporal and frontal neuronal circuits, possibly utilized by the epileptogenic process.

Adolescent↗

Blimp-1, a novel zinc finger-containing protein that can drive the maturation of B lymphocytes into immunoglobulin-secreting cells.

We describe a novel gene, Blimp-1 (for B lymphocyte-induced maturation protein), transcripts of which are rapidly induced during the differentiation of B lymphocytes into immunoglobulin secretory cells and whose expression is characteristic of late B and plasma cell lines. The 856 amino acid open reading frame contains five Krüppel-type zinc finger motifs and proline-rich and acidic regions similar to those of known transcription factors. Serological studies show an approximately 100 kd protein that localizes to the nucleus. Stable or transient transfection of Blimp-1 into B cell lymphoma lines leads to the expression of many of the phenotypic changes associated with B cell differentiation into an early plasma cell stage, including induction of J chain message and immunoglobulin secretion, up-regulation of Syndecan-1, and increased cell size and granularity. Thus, Blimp-1 appears to be a pleiotropic regulatory factor capable of at least partially driving the terminal differentiation of B cells.

Amino Acid Sequence↗

Remeasurement of ions using quadrupolar excitation Fourier transform ion cyclotron resonance spectrometry.

Ions formed by a single laser desorption event can be remeasured more than 500 times in a Fourier transform ion cyclotron resonance spectrometer. Quadrupolar excitation and collisional axialization are used to move ions located in any region of the ICR cell to the center of the cell, where they can be effectively detected. With this method, the signal from ions formed by a single laser desorption event is averaged for 200 remeasurement cycles with an efficiency in excess of 99.5% per cycle. Collisions of ions with helium are found to give higher remeasurement efficiencies than collisions with methane, due to reduced scattering losses by the lighter collision gas. With this method, ions that are stored in the analyzer cell for more than 1 hour can be detected. This technique is shown to be compatible with high-resolution data acquisition. Ions formed by one laser desorption event are remeasured at eight bandwidths, demonstrating low-resolution, wide-mass-range analysis and high-resolution, narrow-mass-range analysis of the same group of ions.

Amino Acid Sequence↗

Monitoring during supratentorial surgery.

Electroneurophysiological monitoring is employed during various supratentorial surgical procedures. EEG and evoked potential monitoring are used to detect and to facilitate the timely correction of cerebral ischemia during carotid endarterectomy and aneurysm surgery. Direct cortical recording and stimulation is used to identify areas or cortex that would be likely to produce clinical deficits if removed. Electrocorticography is used to identify epileptogenic cortex intraoperatively during surgical treatment of epilepsy.

Brain Ischemia↗

Measurement and chromatographic characterization of prodynorphin-derived peptides in the guinea-pig ileum.

Guinea-pig ileum was dissected and the mucosa, submucosa and external musculature extracted with aqueous acetic acid for measurement of four prodynorphin-derived peptides, namely dynorphin A 1-8, dynorphin A 1-17, dynorphin B, and alpha-neoendorphin. The peptide-like immunoreactive material extracted from the external musculature was characterized by multi-dimensional chromatographic analysis and compared to synthetic porcine standards. The chromatographic methods utilized were: reversed-phase high performance liquid chromatography (RP-HPLC), using two different eluants; cation exchange high performance liquid chromatography (CE-HPLC) and gel filtration chromatography. The dynorphin A 1-8-like immunoreactive material was homogeneous and coeluted with the standard in all chromatographic modes. The dynorphin A 1-17-like and dynorphin B-like immunoreactive material was heterogeneous but showed a peak that coeluted with synthetic standard in all chromatographic modes. The alpha-neoendorphin-like immunoreactive material also appeared to be heterogeneous with the major component on CE-HPLC coeluting with the synthetic peptide standard while the major component on RP-HPLC eluted differently. It was concluded that the guinea-pig ileum contains immunoreactivity for peptides derived from all coding regions of the prodynorphin gene and that these peptides may be present in multiple immunoreactive forms.

Animals↗

Sequence analysis and expression of an X-linked, lymphocyte-regulated gene family (XLR).

The XLR gene family consists of approximately 10 X-linked genes, the expression of which is regulated in lymphocyte development. Certain members of the gene family are closely linked to the murine xid immune deficiency mutation. Sequence analysis of a cDNA clone pM1 derived from the plasmacytoma MOPC167 showed an open reading frame capable of coding for a protein of 208 amino acids and mol wt 24,000. The lack of a signal peptide or transmembrane region indicates a probable cytoplasmic or nuclear localization for the predicted pM1 protein. The predicted protein shares significant homology with lamins A and C and other members of the intermediate filament family of proteins, and shares features important for the coiled-coil structure proposed for these proteins. Analysis of cDNA clones derived from a presecretory lymphoma and from adult thymus indicates that B and T lymphocytes transcribe a common major mRNA identical to pM1, while other rare transcripts were also identified by these studies. A series of clonal T lymphoma lines representing distinct stages of thymic differentiation showed that, as with B lymphoid tumors, XLR expression is correlated with the maturation of the thymomas.

Amino Acid Sequence↗

High performance liquid chromatographic determination of ketoconazole in human serum.

A reversed-phase high-performance liquid chromatographic (HPLC) method with terconazole as internal standard is described for the rapid analysis of ketoconazole in human serum. Except for diazepam no other drug interfered with the analysis. The lowest reproducible limit of the method was 0.05 mg/l. The coefficient of variation of the procedure was less than or equal to 7.5% over a range of ketoconazole concentrations from 1.0 to 10.0 mg/l and less than or equal to 16.75% over a range from 0.05 to 0.5 mg/l. Comparison with a microbiological method showed good correlation.

Biological Assay↗

Isolation and microsequence analysis of a novel form of neuromedin U from guinea pig small intestine.

A multidimensional chromatographic regimen has been used to isolate and purify a peptide showing immunoreactivity for neuromedin U from guinea pig small intestine. Microsequence Edman N-terminal analysis and C-terminal analysis by enzymatic digestion showed this peptide to be a nonapeptide with the following sequence: H-Gly-Tyr-Phe-Leu-Phe-Arg-Pro-Arg-Asn-NH2. The C-terminal octapeptide of this sequence is the same as porcine NMU-8, and the C-terminal heptapeptide is identical to rat NMU(17-23).

Amino Acid Sequence↗

Isolation and microsequence analysis of guinea pig alpha-neo-endorphin.

A multidimensional chromatographic regimen was used to isolate and purify alpha-neo-endorphin-like immunoreactive material from guinea pig small intestine. Microsequence analysis of the material obtained showed that the sequence of this peptide in guinea pig is the same as that previously reported for pig and rat, namely: H-Tyr-Gly-Gly-Phe-Leu-Arg-Lys-Tyr-Pro-Lys(OH). Thus, the sequence of alpha-neo-endorphin is conserved in all species thus far examined.

Amino Acid Sequence↗