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Biomedical subjects

G Mohr

Publications and source records attributed to G Mohr.

At least 73 records · Page 4Linked to original sources

Group I and group II introns.

Group I and group II introns are two types of RNA enzymes, ribozymes, that catalyze their own splicing by different mechanisms. In this review, we summarize current information about the structures of group I and group II introns, their RNA-catalyzed reactions, the facilitation of RNA-catalyzed splicing by protein factors, and the ability of the introns to function as mobile elements. The RNA-based enzymatic reactions and intron mobility provide a framework for considering the role of primordial catalytic RNAs in evolution and the origin of introns in higher organisms.

Amino Acid Sequence↗

Dural arteriovenous malformations of the ethmoidal region: report of two cases.

Dural arteriovenous malformations of the ethmoidal region are extremely rare. They are usually supplied by the ipsilateral anterior ethmoidal artery with contralateral contribution in about half of the cases. They are characterized by a fistulous nidus within the dura, and their progression seems to involve a retrograde leptomeningeal vascular stasis with formation of varices and venous aneurysms. They have more propensity to rupture than dural malformations in other locations. Two patients who presented with an acute frontal hemorrhage are reported.

Cerebral Angiography↗

The neurospora CYT-18 protein suppresses defects in the phage T4 td intron by stabilizing the catalytically active structure of the intron core.

The Neurospora CYT-18 protein, a tyrosyl-tRNA synthetase, which functions in splicing group I introns in mitochondria, promotes splicing of mutants of the distantly related bacteriophage T4 td intron. In an in vivo assay, wild-type CYT-18 protein expressed in E. coli suppressed mutations in the td intron's catalytic core. CYT-18-suppressible mutations were also suppressed by high Mg2+ or spermidine in vitro, suggesting they affect intron structure. Both the N- and C-terminal domains of CYT-18 are required for efficient splicing, but CYT-18 with a large C-terminal truncation retains some activity. Our results indicate that CYT-18 interacts with conserved structural features of group I introns, and they provide direct evidence that a protein promotes splicing by stabilizing the catalytically active structure of the intron RNA.

Base Sequence↗

Interference in memory for tonal pitch: implications for a working-memory model.

The degree of interference caused by different kinds of stimuli on memory for tonal pitch was studied. Musically trained and untrained subjects heard a sequence of two tones separated by an interval of 5 sec. The tones were either identical in pitch or differed by a semitone. Subjects had to decide whether the tones were identical or not. The interval was filled with tonal, verbal, or visual material under attended and unattended conditions. The results revealed clear group differences. Musically trained subjects' retention of the first test tone was only affected by the interposition of other tones. In contrast, the performance of musically untrained subjects was also affected by verbal and visual items. The findings are discussed in the framework of Baddeley's (1986) working-memory model.

Adult↗

Retrieval of action phrases: the efficacy of verb cues and noun cues.

Memory for noun cues has been shown to be superior to memory for verb cues. This study investigates two factors that might influence this noun-cue superiority effect: pre-experimental associations between the cue and the target, and encoding strategies. Subjects were to study a list of noun-verb phrases. The pre-experimental associations between the two components of the phrases were either symmetric or asymmetric, and either strong or weak. One group of subjects studied the list under a standard learning instruction. The other group was required to enact the phrases. The results show that the noun-cue superiority is modulated by the variation of pre-experimental associations, that enacting considerably improves cued recall performances, and that enacting neither influences the effects of pre-experimental associations nor the efficacy of the two cuetypes.

Adult↗

Integration of a group I intron into a ribosomal RNA sequence promoted by a tyrosyl-tRNA synthetase.

Group I and II introns are mobile elements that propagate by insertion into different genes. Some introns of both types self-splice in vitro by transesterification reactions catalysed by the intron RNA. These transesterifications are reversible, and it has been suggested that reverse splicing followed by reverse transcription and recombination with genomic DNA may be a mechanism for intron transposition. In vivo the splicing of many, if not all, group I and II introns requires protein factors, which may facilitate correct folding of the intron RNAs. Here we show that the Neurospora mitochondrial large rRNA intron, a group I intron that is not self-splicing in vitro, undergoes reverse splicing in a reaction promoted by the CYT-18 protein, the Neurospora mitochondrial tyrosyl-tRNA synthetase, which is required for splicing the intron in vivo. In contrast to known RNA-catalysed reverse splicing reactions, this protein-assisted reverse splicing is sufficiently rapid to compete with forward splicing at low RNA concentrations under physiologically relevant conditions, including high GTP and low Mg2+ concentrations. Our results indicate that proteins that promote splicing could contribute to intron mobility by promoting reverse splicing in vivo.

Base Sequence↗

The Neurospora mitochondrial tyrosyl-tRNA synthetase is sufficient for group I intron splicing in vitro and uses the carboxy-terminal tRNA-binding domain along with other regions.

Neurospora mitochondrial tyrosyl-tRNA synthetase (mt tyrRS), which is encoded by nuclear gene cyt-18, functions in splicing of group I introns in mitochondria. Here, we overproduced functional cyt-18 protein in Escherichia coli and purified it to near homogeneity. The purified protein has splicing and tyrRS activities similar to those of cyt-18 protein isolated from mitochondria and is by itself sufficient to splice the mitochondrial large rRNA intron in vitro. Structure-function relationships in the cyt-18 protein were analyzed by in vitro mutagenesis. We confirmed that a small amino-terminal domain not found in bacterial tyrRSs is required for splicing activity, but not tyrRS activity. Two linker insertion mutations, which disrupt the predicted ATP-binding site, completely inhibit tyrRS activity but leave substantial splicing activity. Finally, deletions or linker insertion mutations in the putative carboxy-terminal tRNA-binding domain inhibit both tyrRS and splicing activities, although some have differential effects on the two activities. Our results show that the normal catalytic activity of the cyt-18 protein is not required for splicing and are consistent with the hypothesis that the protein functions by binding to the precursor RNA and facilitating formation of the correct RNA structure. Regions required for splicing are distributed throughout the cyt-18 protein and overlap, but are not identical to, regions required for tyrRS activity. The finding that the putative carboxy-terminal tRNA-binding domain is required for both tyrRS and splicing activities suggests that the mechanism for binding the intron has similarities to the mechanism for binding tRNA(Tyr).

Adenosine Triphosphate↗

Improved transformation frequency and heterologous promoter recognition in Aspergillus niger.

Wild-type strains of Aspergillus niger were transformed with integrative vectors. The number of stable transformants varied from approximately 20-30/micrograms up to 17,000/micrograms using acetamide and hygromycin B selection, respectively. The introduction of deletions of 5' and 3' non-coding regions of the acetamidase gene (amdS+) revealed that these sequences influenced the number of transformants. The molecular characterization of A. niger transformants revealed that several copies of the vectors were tandemly integrated into the nuclear DNA. These oligomers were stably inherited, even after 100 days of growth on non-selective medium. The expression of the vector-encoded genes was confirmed by evidence from the mRNAs and corresponding proteins encoded by the selectable marker genes.

Acetamides↗

Surgical management of giant pituitary adenomas.

During the past 25 years, 77 giant pituitary adenomas have been treated surgically, including suprasellar extensions of type C in 66 cases and of type D in 11 cases. Non-secreting adenomas were present in 53 and secreting adenomas in 24 cases. All patients except 3 presented with significant visual field defects; including bitemporal hemianopia, superior quadranopia or unilateral temporal hemianopia, contralateral blindness in 73% of the cases, and one case with sudden bilateral blindness due to acute pituitary apoplexy. A single transsphenoidal procedure was carried out in 74% of the patients while 11 patients (7%) required re-operations for recurrent or residual tumor. Only 3 patients required a subsequent transcranial procedure. Complications included 1 CSF-leak, 1 empty-sella syndrome and 4 fatal post-operative hematomas. We prefer the transsphenoidal route even in very large or giant pituitary adenomas, since it allows rapid and adequate decompression of the optic nerves and chiasm, avoids major pituitary insufficiency in 60% of the cases and is associated with low morbidity-mortality rates.

Adenoma↗

Vertebro-PICA aneurysms: midline suboccipital approach and laminectomy of the atlas.

Vertebro-PICA aneurysms represent a particular technical challenge because of the extremely narrow operative field and the presence of numerous vital neural and vascular structures. The lack of exposure still remains the limiting factor in most cases. During the 9-year period from January 1980 to October 1989, 8 vertebro-PICA aneurysms have been treated microsurgically. Of these, 2 underwent a pure suboccipital approach while 6 underwent a midline suboccipital approach with deliberate removal of the arch of the atlas in the park bench position. Seven patients did well and regained full activities while one patient died from complications related to vasospasm with brainstem infarction. One patient developed symptomatic obstructive dilation of the fourth ventricle requiring ventriculo-cisternostomy. The authors recommend the midline suboccipital approach with deliberate C1-laminectomy in ventrolateral decubitus for vertebro-PICA aneurysms. The main advantages are: constant access to the proximal vertebral artery, less medullary retraction in ventrally located aneurysms, improved exposure of the laterobulbar cisterns and the lateromedullary and tonsillar segments of the PICA, thus facilitating dissection of the aneurysm.

Adult↗

Evaluation of vasospasm secondary to subarachnoid hemorrhage with technetium-99m-hexamethyl-propyleneamine oxime (HM-PAO) tomoscintigraphy.

Vasospasm of intracranial vessels is difficult to diagnose on clinical ground alone. Still, a clear diagnosis is important because it can impact on surgical timing; and also because it can help evaluate new treatments. Fifteen patients with sub-arachnoid hemorrhage secondary to aneurysm rupture were submitted to a total of 26 tomographic technetium-99m-hexamethyl-propyleneamine oxime (99mTc-HM-PAO) brain examinations that were correlated with temporally close (generally less than 24 hr) angiography or transmission computed tomography (TCT). Nine of 10 angiographically confirmed episodes of spasm and 6 of 6 infarcts seen on angiography or TCT were correctly diagnosed with 99mTc-HM-PAO. One normal scintigraphic exam was angiographically doubtful, one positive 99mTc-HM-PAO study was normal on angiography (sub-radiologic spasm?), one technically poor scintigraphy was positive for spasm on angiograms, and eight exams were normal for spasm with all modalities. We had agreement between tests in 23 of 26 series of exams (88%) obtained in 15 patients. We think that 99mTc-HM-PAO tomography should be useful for the evaluation of patients with suspected vasospasm.

Adult↗

Nimodipine treatment in poor-grade aneurysm patients. Results of a multicenter double-blind placebo-controlled trial.

A multicenter, randomized placebo-controlled double-blind trial of nimodipine in poor-grade aneurysm patients was carried out in 17 Canadian hospitals. Of 188 patients enrolled in the trial, 32 were excluded for protocol violations and two were excluded due to statistical considerations, leaving 154 patients for valid outcome analysis. Nimodipine treatment was associated with a significantly better outcome (p less than 0.001): 21 (29.2%) of 72 nimodipine-treated patients had a good outcome at 3 months after subarachnoid hemorrhage (SAH) compared to eight (9.8%) of 82 placebo-treated patients. Delayed ischemic deficits from vasospasm alone were significantly less frequent in the nimodipine group (p less than 0.05) with permanent deficits occurring in five nimodipine-treated patients (6.9%) and in 22 placebo-treated patients (26.8%). Improvement in the good outcome rate and reduction in delayed ischemic deficits from vasospasm alone occurred in both Grade 3 and 4 patients, with no difference between nimodipine- and placebo-treated patients being found in Grade 5 patients. Repeat angiography after Day 4 was carried out in 124 patients. There was no significant difference in the incidence of moderate or severe diffuse spasm, which was seen in 64.3% of nimodipine-treated patients and 66.2% of placebo-treated patients. The authors conclude that nimodipine treatment in poor-grade patients with SAH results in an increase in the number of good outcomes and a reduction in the incidence of delayed neurological deterioration due to vasospasm. This effect occurs by a mechanism other than prevention of large-vessel spasm as visualized on angiography.

Adolescent↗

Selective vestibular neurectomy through the posterior fossa in Ménière's disease.

The authors report on a series of 18 patients operated through the posterior fossa approach for selective vestibular neurectomy. The indication for surgery consisted of intractable vertigo in cases of Ménière's disease. Results were excellent with a 94% cure of vertigo and 100% improvement. Postoperative hearing results were good with 78% of patients maintaining their discrimination score and 94% their pure tone average threshold. The results and the advantages of this approach are discussed and compared with the known procedures as reported in the literature.

Adult↗

Prolonged unemployment and depression in older workers: a longitudinal study of intervening variables.

In this study, unemployed blue-collar workers over the age of 45 (N = 51) filled out a questionnaire in 1975 and in 1977. It was shown that prolonged unemployment or re-unemployment leads to depression, reduced hope, and financial problems, although none of these factors leads to prolonged unemployment. Being employed or retired leads to a reduction of depression and financial problems. Problems associated with the daily hassles of unemployment, such as financial problems and disappointed hope play a role in the development of depression with prolonged unemployment. Potential third variables that could cause both unemployment and depression--such as internal/external control, passivity, sickness, and age--do not affect the effect of unemployment on depression.

Depression↗

Microvascular anatomy of Heubner's recurrent artery.

The microvascular anatomy of Heubner's recurrent artery (RAH) was studied in 50 human brains (100 hemispheres) using acrylic paint under the operative microscope. The recurrent artery of Heubner was always found as a single vessel in 28 cases (28%) and multiple vessels in 72% (double vessels in 48%, triple in 23% and quadruple in 1%). Altogether 197 RAH were found in 100 hemispheres, averaging 1.97 arteries per hemisphere. In 44 instances, it originated from the proximal part of the A1-segment of the anterior cerebral artery. The diameters of the RAH ranged from 0.4 to 1.5 mm. Their vascular territory was variable. Four groups of distributing branches were found in the RAH: frontal and hypothalamic, olfactory, perforating and sylvian-fissure branches. In 12 hemispheres, anastomoses were found between the perforating branches of the RAH and the middle cerebral artery. In five cases (5%) anastomoses were present between the perforating branches of the MCA and the olfactory branch of the RAH. In one case (1%), an anastomosis was found between two RAH.

Cerebral Arteries↗

Hemodynamic and metabolic effects of cerebral revascularization.

Pre- and postoperative positron emission tomography (PET) was performed in six patients undergoing extracranial to intracranial bypass procedures for the treatment of symptomatic extracranial carotid occlusion. The six patients were all men, aged 52 to 68 years. Their symptoms included transient ischemic attacks (five cases), amaurosis fugax (two cases), and completed stroke with good recovery (one case). Positron emission tomography was performed within 4 weeks prior to surgery and between 3 to 6 months postoperatively, using oxygen-15-labeled CO, O2, and CO2 and fluorine-18-labeled fluorodeoxyglucose. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rates for oxygen and glucose (CMRO2 and CMRGlu), and the oxygen extraction fraction (OEF) were measured in both hemispheres. Preoperatively, compared to five elderly control subjects, patients had increased CBV, a decreased CBF/CBV ratio, and decreased CMRO2, indicating reduced cerebral perfusion pressure and depressed oxygen metabolism. The CBF was decreased in only one patient who had bilateral carotid occlusions; the OEF, CMRGlu, and CMRO2/CMRGlu and CMRGlu/CBF ratios were not significantly different from control measurements. All bypasses were patent and all patients were asymptomatic following surgery. Postoperative PET revealed decreased CBV and an increased CBF/CBV ratio, indicating improved hemodynamic function and oxygen hypometabolism. This was associated with increased CMRO2 in two patients in whom the postoperative OEF was also increased. The CMRGlu and CMRGlu/CBF ratio were increased in five patients. Changes in CBF and the CMRO2/CMRGlu ratio were variable. One patient with preoperative progressive mental deterioration, documented by serial neuropsychological testing and decreasing CBF and CMRO2, had improved postoperative CBF and CMRO2 concomitant with improved neuropsychological functioning. It is concluded that symptomatic carotid occlusion is associated with altered hemodynamic function and oxygen hypometabolism. Cerebral revascularization results in decreased CBV, indicating improved hemodynamic reserve, but does not consistently improve oxygen metabolism.

Aged↗