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Biomedical subjects

T H Williams

Publications and source records attributed to T H Williams.

At least 109 records · Page 6Linked to original sources

Morphological differentiation of a murine neuroblastoma clone in monolayer culture induced by dexamethasone.

Dexamethasone induces morphological differentiation in murine neuroblastoma cells in culture. The percentage of differentiated cells depends on the concentration of dexamethasone in the medium and duration of treatment. After drug removal (with or without replating), many cells maintain their differentiated phenotype. Dexamethasone-treated cells have larger soma and contain more protein. Dexamethasone also produces a concentration-dependent inhibition of population growth. Growth inhibition is complete by 2 days following treatment with dexamethasone 50 micrograms/ml. Complete growth inhibition is achieved prior to the complete expression of morphological differentiation. Androstenedione, testosterone, and 17-beta-estradiol--all steroids without glucocorticoid activity--have no differentiating effect, although they inhibit growth or cause cell death at higher concentrations.

Animals↗

Intracerebral displacement of basal ganglia following septal cannulation.

The effects of septal cannulation on the displacement of basal ganglia form the basis of the present communication. In experimental rats, in which a cannula is chronically implanted for 30 days between the medial and lateral septal nuclei by stereotaxic procedures, considerable shift of the basal ganglion is always observed on the operated side. The displacement takes place along the long axis of the ganglion either rostrally or caudally. Besides gross asymmetry in their relative sizes, no histological differences are observed between the ganglia of the two sides. Control animals, in which the cannula is withdrawn immediately after the septal lesion, manifest similar, but less pronounced movements of the basal ganglia. The probable underlying mechanisms for such intracerebral shifts are discussed and the role of indirect mechanical forces is outlined. The extraordinary degree of plasticity of the subcortical nuclear masses in terms of mobility is also emphasized.

Animals↗

Production of a novel red pigment, rubrolone, by Streptomyces echinoruber Sp. Nov. II. Chemistry and structure elucidation.

Streptomyces echinoruber sp. nov. produces several red pigments. The major component, rubrolone, has been identified as 8(R),9(R),10(S),10a(R)-tetrahydro-9,10,10a,11-tetrahydroxy-3,8-dimethyl-1-propyl-6aH(S)-pyrano[2",3":5',4]furo[2',3':5,6]azuleno[2,3-c]pyridine-5,13-dione (1) by single crystal X-ray analysis of a suitable derivative. A second pigment, B, is probably structurally closely related.

Chemical Phenomena↗

Early ultrasound examination in antenatal care.

Ultrasound examination was done on 442 women early in pregnancy. If there was a discrepancy the date of delivery calculated from ultrasound readings was preferred to that calculated by traditional means. As a result of this policy induction for planned caesarean section was postponed or cancelled in 10.4% of cases. In 9.7% of women the menstrual history was unreliable and the ultrasound measurement was used to estimate the date of delivery. Thus in 21.1% of pregnancies the early ultrasound measurement decided when or whether labour was to be induced. In women induced for postmaturity there was no increase in prolonged labour or need for caesarean section. There were no cases of neonatal respiratory distress and neonatal jaundice was less common than it was when the onset of labour was spontaneous. This evidence suggests that neonatal jaundice is not caused by induction of labour or by the agents used. The low frequency of jaundice in this series is thought to be due to accurate prediction of the expected date of delivery and consequent exclusion of premature babies born to "postmature" women.

Cephalometry↗

Evidence for dopamine-storing interneurons and paraneurons in rhesus monkey sympathetic ganglia.

In order to study and quantify the small, intensely fluorescent (SIF) cells and to examine their synaptology, the superior cervical sympathetic ganglia of rhesus monkeys were examined by a sequential glyoxylic acid (GA) monoamine fluorescence and electron microscopic technique. Correlated data concerning the sensitivity of the ganglia to dopamine were gathered by measuring the rise in cyclic AMP levels following incubation in vitro with exogenous dopamine. Cyclic AMP levels after incubation for 12 min with 50 micron dopamine showed marked increases, averaging 288% of control values. This indicates that these ganglia contain a dopamine receptor-adenylate cyclase complex. The number of SIF cells per mg of tissue was about half that found in the cow and rabbit, and only 1% of the number observed in the rat. Morphological data support the view that, in this species, there are almost equal numbers of type I (hypothesized interneuron) and type II (paraneuron) SIF cells. Presumptive SIF cell efferent synapses were observed by electron microscopy, the postsynaptic elements being dendritic spines or very fine nerve processes.

Animals↗

Acute scrotal swelling in Henoch-Schönlein syndrome.

A review of the literature regarding scrotal swelling in Henoch-Schönlein purpura is compared with our own experience at the Mayo Clinic over the previous ten years. Of 59 boys seen with Henoch-Schönlein purpura, 9 were noted to have scrotal swelling, and in 4 the presentation was of sufficient severity to suggest torsion. Two of these 4 were managed conservatively, and spontaneous recovery resulted. Surgical exploration of the scrotum in the other 2 revealed evidence of vasculitis in both and the possibility of torsion of appendix epididymis in 1. In patients with Henoch-Schölein purpura and scrotal pain and swelling, a conservative approach with cautious observation appears justified.

Acute Disease↗

Ultrastructural aspects of bilirubin encephalopathy in cochlear nuclei of the Gunn rat.

The cochlear nuclei of homozygous Gunn rats aged 2 days to 7 months were examined. Ultrastructural abnormalities were observed in all age groups studied, including 2 and 4 days old animals. Mitochondrial alterations are amont the earliest manifestations of bilirubin encephalopathy (2 days). In mitochondria of large neurons, vacuoles were found which contained increasing (with age) collections of alpha and beta glycogen particles. Some of the larger 'ex-mitochondrial sacs' appear to have been caught at the point of disruption, with glycogen-filled vacuoles in close proximity. Dilated profiles of rough ER also contained glycogen particles. In the cytoplasm of the same large neurons, elaborate myelin figures surrounded tongues of cytoplasm, vacuoles and degenerative elements. Reconsideration of previous morphological and biochemical observations in the light of the present findings makes it appear very likely that bilirubin primarily affects membrane function, especially in mitochondria.

Animals↗

A method for studying glyoxylic acid induced fluorescence and ultrastructure of monoamine neurons.

Inasmuch as precise correlations of light- and electronmicroscopy are crucial for understanding biostructure, it seemed necessary to bring together the advantages of the glyoxylic acid (GA) method (for inducing monoamine fluorescence) and electron microscopy. A combined fluorescence and electron microscope method using GA is introduced. The brain is perfused by 2% GA in Krebs-Ringer bicarbonate buffer (pH 7.0) and this solution is followed by 4% paraformaldehyde containing 0.5% glutaraldehyde in Sorensen's phosphate buffer (pH 7.4). Sections are cut by cryostat or by vitratome and incubated in 2% GA in phosphate buffer (pH 7.0). Using fluorescence microscopy, features of interest are sketched and/or photographed. Afterwards, the same or subsequent section is processed for electron microscopy. Since axons of catecholamine-containing neurons (as well as their perikarya and terminals) are visualized by GA, the recommended procedure expands the range of studies concerning monoamine neurons that can now be carried out effectively.

Animals↗

Synthesis of tetrazole ribonucleosides and their evaluation as antiviral agents.

Synthesis of 1-beta-D-ribofuranosyltetrazole and two 5-substituted derivatives, i.e., the 5-carboxamide and 5-acetamide, is described. The stereochemical structure of the parent tetrazole ribonucleoside has been established by means of nuclear Overhauser effect and x-ray crystallography. By analogy to the parent compound, the two 5-substituted tetrazole nucleosides are also assigned the beta configuration on the basis of the NMR coupling constant of the anomeric proton and the site of N-ribosylation is determined by 13C NMR studies. Results are also presented on antiviral testing of these synthetic tetrazole nucleosides against influenza A2/Asian/J-305 virus infection in mice.

Animals↗

Effect of surgical trauma on the endogeneous heme iron in the brain.

Paucity of electron-microscopic studies on the fate of endogenous heme iron, released as a result of planned surgery, in the central nervous system warranted the present work. During investigations of neuronal plasticity in the cat, an experimental model, in which the proximal cut end of the vagosympathetic trunk was rerouted into the diencephalon, presented an ideal substrate for studying this problem. At 3 months, the brain tissue containing the implant was processed for light and electron microscopy and histochemistry. Under light microscopy, Prussian-blue-positive, dense cytoplasmic aggregates were visible within the macrophages. The cells were mostly clustered around the junctional area between the central and peripheral nerve elements. Electorn-microscopic findings were highly characteristic and distinguished the macrophages from the surrounding neural elements by their rich content of electron-dense granules. While the latter were mostly scattered as free cytoplasmic particles, large aggregates of the same were also observed inside the lysosomes. Besides, a few inclusions were seen within astrocytic processes, close to the plasma membranes. At higher magnifications, the particles revealed the characteristic internal subunit structure of ferritin micelles. The uptake of hemoglobin and its subsequent conversion of ferritin within the macrophages and astrocytic processes are discussed at subcellular level in the light of other available studies.

Animals↗

Histofluorescence characteristics and quantification of small intensely fluorescent (SIF) cells in sympathetic ganglia of several species.

Small intensily fluorescent (SIF) cells in the superior cervical ganglion of the cow, cat, rabbit, rat, guinea pig and monkey were studied, using the glyoxylic acid monoamine fluorescence method. SIF cell populations per mg ganglion tissue showed great species variation. The greatest numbers of SIF cells per mg were found in the rat (380+/-30 per mg). Intermediate numbers (76+/-20 per mg) were found in the guinea pig; and SIF cells in other species were much more sparsely distributed (less than 10 per mg). Two types of SIF cell were identified. Type I cells have long (up to 200 mu) processes which ramify among the principal ganglionic neurons, and this type often occurs singly; whereas type II cells tend to occur in clusters near blood vessels in the interstitial or subcapsular regions of the ganglion. As a general hypothesis we propose that type I SIF cells are interneurons whereas type II SIF cells operate through a neurosecretory mechanism.

Animals↗

An improved method for perfusion fixation of neural tissues for electron microscopy.

A method employing vascular perfusion for improved preservation of biological ultrastructure is described, and its effectiveness demonstrated for mammalian nervous tissues. Following a physiological saline flush into the aorta, hydrogen peroxide and glutaraldehyde in phosphate buffer are perfused. After buffer rinses, tissue blocks are postfixed in osmic acid and potassium ferrocyanide. The success rate is enhanced greatly by close attention to details of perfusion technique. Advantages of the method include more uniform and complete preservation. In particular, superior images of membranous elements, glycogen granules and basal laminar material are achieved. Adjustments in osmolality may render the procedure suitable for nonmammalian forms and other tissues.

Animals↗

Changes in cholinergic synaptic vesicle populations and the ultrastructure of the nerve terminal membranes of Narcine brasiliensis electron organ stimulated to fatigue in vivo.

Narcine brasiliensis electric organ was stimulated to fatigue in vivo. Electrical display of organ output and biochemical assay of bound acetylcholine (ACh) and ATP in isolated vesicles were used to assess the state of fatigue relative to denervated control organs of the same fish. A morphometric analysis of the fate of the synaptic vesicle populations in the nerve terminals was carried out. Statistically significant morphological changes in vesicle populations and plasma membranes were observed between control and fatigued electroplaque stacks from individual fish. Pooled data from several fish were used to evaluate the possible role of the different vesicle types in neurotransmission. Fatigue resulted in the loss of 49% of the total vesicle population and a 76% loss of vesicles with bound calcium (Ca). An approximately equivalent increase in the nerve-terminal plasma membrane area was measured. This was predominantly in the form of fingerlike protrusions and/or invaginations of the terminals which were present in the control organs but which were significantly increased by stimulation. Vesicle attachments to the nerve terminal membrane were reduced by 90%. This suggests that the failure in transmission may be due to reduction in the number of vesicles which are loaded with transmitter and can attach to the terminal membrane. The Ca-binding capacity of the lost vesicles was not transferred to the plasma membranes. This result was interpreted as support for the hypothesis that vesicle-bound ATP provides the Ca-binding site.

Acetylcholine↗

Antimetabolites produced by microorganisms. XII (S)-alanyl-3-[alpha-(S)-chloro-3-(S)-hydroxy 2-oxo-3-azetidinylmethyl]-(S)-alanine, a new beta-lactam containing natural product.

(S)-Alanyl-3-[alpha-(S)-chloro-3-(S)-hydroxy-2-oxo-3-azetidinylmethyl]-(S)-alanine was isolated from a fermentation broth of an unidentified Streptomyces species 372 A. The structure was determined by single crystal X-ray diffraction analysis. The substance inhibits the growth of several strains of gram-positive and gram-negative bacteria in a chemically defined medium but growth inhibition is relieved by addition of L-glutamine to the medium.

Alanine↗