Search PubMed⌕ Search

Biomedical subjects

A Newman

Publications and source records attributed to A Newman.

At least 55 records · Page 3Linked to original sources
PubMed1995

Effect of vestibular nerve section on cytochrome oxidase activity in the vestibular ganglion cells of the squirrel monkey.

Cytochrome oxidase (CO) activity of the vestibular ganglion cells of the squirrel monkey was demonstrated histochemically under normal and experimental conditions. Under general anesthesia, right vestibular nerve section was performed on adult squirrel monkeys between the vestibular ganglion and brain stem. The left side was left intact and was used as a within-animal normal control. One squirrel monkey that did not undergo vestibular nerve section was also included in the normal group. Following a survival period of seven months, neurons in the vestibular ganglion of both sides were examined. In the normal control sides, a significant negative correlation between the size of the neuron and its optical density for CO stain was observed. Many neurons in the vestibular ganglion survived after vestibular nerve section, but their cell sizes and optical densities of CO stain decreased compared with those of the control side.

Animals↗
PubMed1995

The sensitivity of leukemic bone marrow to simvastatin is lost at remission: a potential purging agent for autologous bone marrow transplantation.

BACKGROUND: Autologous bone marrow transplantation (ABMT) is frequently used in the treatment of malignant disease but carries the risk of reintroducing tumor cells into the patient. Methods are required for removing malignant cells from harvested bone marrow (BM) without impairing hematopoietic reconstitution. We have shown that simvastatin is toxic to leukemic progenitor cells at a concentration that conserves normal BM progenitors and may be of use clinically as a novel BM purging agent. METHODS: A two-stage culture system was used to compare the effects of simvastatin on both normal BM progenitor and primary acute myeloid leukemia (AML) cells. AML cells and normal BM mononuclear cells were incubated for 18 hours in suspension culture with 10 micrograms per mL simvastatin and the numbers of surviving clonogenic progenitor cells assayed in semisolid agar culture. RESULTS: Following simvastatin treatment of 18 AML cell populations, the mean surviving fraction of progenitor cells was 21.3 +/- 4.8% ( +/- standard error of the mean [SEM]). In contrast, the mean survival of normal BM progenitors from 16 donors was 89.6 +/- 8.6% ( +/- SEM). Samples were taken from 6 AML patients before treatment and after remission of disease had been induced by chemotherapy. In 5 of these cases the AML sample was significantly more sensitive to simvastatin than the remission sample, 4 of the 5 showed > 80% difference in progenitor cell survival. CONCLUSIONS: AML progenitor cells are sensitive to a short-term exposure to simvastatin that spares normal BM hematopoietic progenitor cells. We conclude that simvastatin may be an effective in vitro purging agent in ABMT for AML.

Acute Disease↗
PubMed1994

RNA splicing. Activity in the spliceosome.

In the active spliceosome, U2, U5 and U6 small nuclear RNAs form a network of interactions with the RNA substrate. U6 snRNA is closely implicated in the catalysis of splicing.

Animals↗
PubMed1994

Small nuclear RNAs and pre-mRNA splicing.

Genetic and biochemical studies have recently shown that the splice sites in nuclear pre-mRNAs are aligned for the transesterification reactions through a collaboration between U5 and U6 small nuclear RNAs, which form the heart of a network of RNA-based interactions in the active spliceosome.

Animals↗
PubMed1994

Selective inhibition of primary acute myeloid leukaemia cell growth by simvastatin.

Primary human acute myeloid leukaemic (AML) cells from bone marrow (BM) and peripheral (PB), the human myeloblastic leukaemia cell line (HL60) and normal human BM mononuclear cells were cultured in serum-free medium. The survival of progenitor cells from normal BM, HL60 and AML cell populations was reduced over a range of concentrations of simvastatin. This dose response relationship was more pronounced in HL60 and AML cell cultures, indicating greater sensitivity of AML progenitor cells compared with normal BM progenitors. Short-term exposure (18 h) to a range of concentrations of simvastatin showed the same differential response between leukaemic and normal BM cells in terms of clonogenicity. At a concentration of 10 micrograms/ml progenitor cell survival remained above 65% for normal BM while at this concentration leukaemia progenitor cell survival fell below 25% of the untreated values. The differential effect of simvastatin on normal and leukaemic progenitor cells may have value in the clinical management of AML. The possible use of simvastatin, or related drugs, as adjuvants to conventional chemotherapy including in vitro BM purging, merits consideration.

Acute Disease↗
PubMed1994

Selective inhibition of primary acute myeloid leukaemia cell growth by lovastatin.

Primary human acute myeloid leukaemic (AML) cells from bone marrow (BM) and peripheral blood (PB), the human myeloblastic leukaemia cell line (HL60) and normal human BM mononuclear cells were cultured in serum-free medium. The survival of progenitor cells from normal BM, HL60 and AML cell populations was reduced over a range of concentrations of lovastatin. This dose response relationship was more pronounced in HL60 and AML cell cultures, indicating greater sensitivity of AML progenitor cells compared with normal BM progenitors. Short-term exposure (18 h) to a range of concentrations of lovastatin showed the same differential response between leukaemic and normal BM cells in terms of clonogenicity. At a concentration of 10 micrograms/ml progenitor cell survival remained above 65% for normal BM while at this concentration leukaemia progenitor cell survival fell below 25% of the untreated values. The differential effect of lovastatin on normal and leukaemic progenitor cells may have value in the clinical management of AML. The possible use of lovastatin, or related drugs, as adjuvants to conventional chemotherapy including in vitro BM purging, merits consideration.

Adult↗
PubMed1993

Opioid receptor antagonist nalmefene stereospecifically inhibits glutamate release during global cerebral ischemia.

The opioid receptor antagonist nalmefene improves cellular bioenergetics and attenuates the reduction in tissue glutamate levels after global cerebral ischemia/reperfusion. The latter finding suggests that nalmefene might inhibit glutamate release during ischemia. To test this hypothesis, we used microdialysis techniques to examine the effect of nalmefene pretreatment on extracellular excitatory amino acid levels during global cerebral ischemia in rats. Saline, (-)-nalmefene (20, 100 or 500 micrograms/kg) or the inactive nalmefene enantiomer (+)-nalmefene (100 micrograms/kg) were given 15 min prior to induction of ischemia using a multi-vessel occlusion model. Pretreatment with (-)-nalmefene decreased peak dialysate glutamate in a dose-dependent fashion as compared to saline-treated controls, whereas (+)-nalmefene had no effect. These results suggest that opioid receptors may modulate glutamate release during ischemia and that inhibition of excitatory amino acid release may contribute to the protective actions of opioid receptor antagonists in cerebral ischemia.

Animals↗
PubMed1992

Afferent innervation of the vestibular nuclei in the chinchilla. I. A method for labeling individual vestibular receptors with horseradish peroxidase.

A new method was developed for specific labeling of primary vestibular afferent fibers from selected end-organs with horseradish peroxidase (HRP) applied extracellularly in the inner ear space. In 48 chinchillas, labeling was performed successfully in all animals by scratching the surface of the sensory end-organ of interest with an electrolytically sharpened needle and replacing the fluid in the vestibule with 30% HRP solution. Merely replacing the vestibular fluid (endo- and perilymph) with HRP did not label the ganglion cells or the afferent fibers in the brain stem. The specificity of labeling was verified by histological inspection of the ganglion cells and nerve fibers innervating the damaged and intact receptors. When the posterior semicircular canal and saccular receptors were scratched, labeled fibers and ganglion cells were found in the nerve and ganglion rostrodorsally and caudoventrally, respectively. Labeled ganglion cells from different superior vestibular nerve (SVN) receptors did not show as clear a segregation pattern as did labeled receptors from the inferior vestibular nerve (IVN). Once inside the brain stem, labeled fibers from the SVN receptors were rostral to those from the IVN receptors. The fibers of the vestibular root divided into an ascending and a descending branch which formed the vestibular tract. Labeled fibers from the SVN receptors divided rostrolaterally to those from the IVN receptors. In the vestibular tract, fibers coursed in different locations according to the receptor of origin. Fibers from the utriculus were lateral to those from the horizontal semicircular canal, which were lateral to those from the anterior semicircular canal. Fibers from the sacculus were lateral to those from the posterior semicircular canal.

Afferent Pathways↗
PubMed1992

Afferent innervation of the vestibular nuclei in the chinchilla. II. Description of the vestibular nerve and nuclei.

The morphological characteristics of the vestibular nuclei of the chinchilla were studied in horizontally cut serial sections of the brain stem. Horseradish peroxidase labeling allowed unambiguous delineation of the vestibular nuclei and areas of innervation by the vestibular afferent fibers. The cytoarchitecture of the vestibular nuclei was documented with the aid of camera lucida drawings and quantitatively evaluated with computerized methodology. The cellular groups identified in other species were found in the chinchilla. The superior vestibular nucleus (SN) originated ventromedial to the mesencephalic tract and nuclei of the trigeminal nerve. This nucleus contained medium-sized cells with a central group of larger cells (20-34 microns in diameter). It received its maximum vestibular innervation caudally in the ventrolateral and dorsal aspects of the nucleus. Fibers projected to the SN in bundles with thick fibers surrounded by thin ones. The lateral vestibular nucleus (LN) originated 0.9-1.2 mm below the rostral aspect of the vestibular area. It was ventrocaudal to the SN and contained many large cells with diameters of 45-60 microns. The LN was innervated mainly in the ventrocaudal aspect by oblique and transverse fibers that formed a dense mesh. The medial vestibular nucleus (MN) originated 0.3-0.6 mm caudal to the beginning of the SN, adjacent to the floor of the IVth ventricle. It extended for 3-4 mm along the SN, LN and descending vestibular nucleus (DN). The MN contained the densest and most homogeneous cells, which had diameters of 10-20 microns. This nucleus received its greatest innervation at the level of the vestibular root. Thin fibers traveled to the MN through the SN and LN. The caudal pole of the nucleus did not receive fibers. The DN originated 1.8-2.5 mm caudal to the origination of the SN, between the caudal LN and the MN. Caudally it replaced the LN. Most of the cells of the DVN were medium-sized, with diameters of 10-20 microns. The main vestibular innervation of the DN was in the lateral aspect of the nucleus. Tertiary fibers projected in small, separate bundles of uniform-sized thick fibers. The interstitial nucleus originated 1.1-1.4 mm from the beginning of the SN. It occupied the center of the vestibular root, 0.8-0.9 mm medial to the root entry zone. It contained a few large cells (greater than 20 microns in diameter), many medium-sized cells, and some small cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1992

Major electrocardiographic abnormalities in persons aged 65 years and older (the Cardiovascular Health Study). Cardiovascular Health Study Collaborative Research Group.

Electrocardiographic abnormalities are often found in older patients, but their prevalence in free-living elderly populations is not well-defined. In addition, the clinical significance of many of these abnormalities is uncertain. The prevalence of major electrocardiographic abnormalities was determined in 5,150 adults aged greater than or equal to 65 years from the Cardiovascular Health Study--a study of risk factors for stroke and coronary heart disease in the elderly. Ventricular conduction defects, major Q/QS waves, left ventricular hypertrophy, isolated major ST-T-wave abnormalities, atrial fibrillation and first-degree atrioventricular block were collectively categorized as major electrocardiographic abnormalities. Prevalence of any major electrocardiographic abnormality was 29% in the entire cohort, 19% among 2,413 participants who reported no history of coronary artery disease or systemic hypertension, and 37% among 2,737 participants with a history of coronary artery disease or hypertension. Prevalence of major electrocardiographic abnormalities was higher in men than in women regardless of history, and tended to increase with age. Major Q/QS waves were found in 5.2%, and more than half were in those who did not report a previous myocardial infarction. Major electrocardiographic abnormalities are common in elderly men and women irrespective of the history of heart disease.

Age Factors↗
PubMed1992

Regeneration of the eighth cranial nerve in the bullfrog, Rana catesbeiana.

The present study was done in order to document the ability of the eighth cranial nerve of the bullfrog (Rana catesbeiana) to regenerate, the anatomic characteristics of the regenerated fibers, and the specificity of projections from individual endorgan branches of the nerve. The eighth cranial nerve was sharply transected between the ganglion cells and the brain stem in 40 healthy bullfrogs and allowed to regenerate. Anatomic studies were performed in these animals a minimum of 3 months postoperatively. Horseradish peroxidase was used to label the whole vestibular nerve or its individual endorgan branches. Labeled regenerated fibers could be identified crossing the site of the nerve section and projecting centrally to the vestibular nuclei in a pattern similar to that of normal frogs. Labeling of individual branches showed that regenerated fibers innervated the same specific areas found in normal frogs. Unlike normal animals, both thick and thin fibers projected to the medial nucleus.

Animals↗
PubMed1992

PET imaging of opiate receptor binding in human epilepsy using [18F]cyclofoxy.

We used [18F]cyclofoxy (CF), a potent opiate antagonist with affinity for mu and kappa receptors, and the Scanditronix PC1024-7B PET scanner to study 14 patients with complex partial seizures (CPS), and 14 normal controls. Epileptic foci were localized by prolonged EEG-video monitoring. EEG was recorded continuously during each scan. Immediately before CF administration, [15O]labeled water was used to measure cerebral blood flow, and showed hypoperfusion ipsilateral to the EEG focus. Blood samples (corrected for radiolabeled metabolites) and tissue time-activity data were acquired over 90 min following bolus CF injection. Anatomic regions were outlined directly on the PET images. A kinetic model was used to derive the total volume of distribution (Vt) in each brain region. Specific binding (Vs) was determined by substracting non-specific binding (Vt) measured in a receptor-poor brain region (occipital cortex). Regions with high Vs included mesial temporal lobes, thalamus, basal ganglia, and frontal cortex. Individual patients appeared to have higher binding in temporal lobe ipsilateral to the EEG focus, but there was no asymmetry for the patients as a group in mean Vt or Vs in anterior mesial, posterior mesial, anterior lateral, posterior lateral temporal cortex, thalamus, basal ganglia, or, for Vt, in regions of low specific binding: occipital lobe, parietal lobe, cerebellum.

Adolescent↗