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Biomedical subjects

M Singer

Publications and source records attributed to M Singer.

At least 235 records · Page 13Linked to original sources

In vitro measurement of cytosol and cell nuclear androgen receptors in male rat brain and pituitary.

An in vitro assay procedure is described for measuring androgen receptor binding in cytosol and cell nuclei of brain and pituitary tissue using [3H]R1881 as ligand. The cell nuclear assay uses the exchange method, which permits assessment of endogenous occupancy of androgen receptors in brain and pituitary. Competition and saturation analysis indicated that [3H]R1881 binding has the specificity and nanomolar affinity expected of an androgen receptor. Moreover, we demonstrated that androgen receptor binding predominated in cytosol from castrated rats and in cell nuclei of male rats treated in vivo with testosterone. Furthermore, as expected, testicular feminized male rats showed low levels of putative androgen receptors in both cytosol and cell nuclei.

Animals↗

In vivo metabolic intermediates of phospholipid biosynthesis in Rhodopseudomonas sphaeroides.

The in vivo metabolic pathways of phospholipid biosynthesis in Rhodopseudomonas sphaeroides have been investigated. Rapid pulse-chase-labeling studies indicated that phosphatidylethanolamine and phosphatidylglycerol were synthesized as in other eubacteria. The labeling pattern observed for N-acylphosphatidylserine (NAPS) was inconsistent with the synthesis of this phospholipid occurring by direct acylation of phosphatidylserine (PS). Rather, NAPS appeared to be kinetically derived from an earlier intermediate such as phosphatidic acid or more likely CDP-diglyceride. Tris-induced NAPS accumulation specifically reduced the synthesis of PS. Treatment of cells with a bacteriostatic concentration of hydroxylamine (10 mM) greatly reduced total cellular phospholipid synthesis, resulted in accumulation of PS, and stimulated the phosphatidylglycerol branch of phospholipid metabolism relative to the PS branch of the pathway. When the cells were treated with a lower hydroxylamine dosage (50 microM), total phospholipid synthesis lagged as PS accumulated, however, phospholipid synthesis resumed coincident with a reversal of PS accumulation. Hydroxylamine alone was not sufficient to promote NAPS accumulation but this compound allowed continued NAPS accumulation when cells were grown in medium containing Tris. The significance of these observations is discussed in terms of NAPS biosynthesis being representative of a previously undescribed branch of the phospholipid biosynthetic sequence.

Hydroxylamine↗

Evaluating alcoholism treatment programs: considerations and caveats.

There are many pitfalls in the design and implementation of treatment evaluations which can be avoided by careful scrutiny of previous efforts. To this end, the author reviews several key methodological and conceptual issues which affect evaluations of treatment outcome. The issue of sampling is discussed with primary attention given to biases resulting from common sampling errors. The measurement of treatment outcome is explored, underscoring the limitations and benefits of employing drinking behavior indices. Suggestions are made to improve follow-up response rates, and a strategy for analyzing follow-up losses is outlined. Finally, a number of frequently overlooked variables which may relate to treatment outcome are reviewed.

Alcohol Drinking↗

The effect of limiting light to the pineal on the rate of forelimb regeneration in the newt.

Newts with bilaterally amputated forelimbs were exposed to either continuous light (LL), total darkness (DD), or continuous light with the dorsal head epithelium painted with an India ink and Nile blue sulfate mixture (LL-II-NBS) that limited light penetration through the skull to the pineal. The LL-II-NBS animals regenerated their forelimbs more slowly then their counterparts in LL.

Animals↗

Partial denervation effects on limb cartilage regeneration.

Partially innervated axolotl arms gave regenerates of reduced size with deficient skeletal element replacement. This deficiency was most pronounced when nerve 4 (the largest of the brachial nerves) estimated to make up 50-60% of forelimb axons was removed by repeated resection. Nerve 3 or 5 removal gave less pronounced reduction deformities in the newly formed regenerate. The dependency of skeletal element formation upon nerves is emphasized but does not follow a strict segmental subtraction in axolotl forelimbs--perhaps because of overlapping innervation of nerves 3, 4, and 5 to all four digits. These effects of partial innervation add tentative support for an hypothesis of neurotome subtraction that was proposed to account for the syndrome of thalidomide abnormalities.

Ambystoma mexicanum↗

Time-dependent effects of vagotomy on pancreatic polypeptide release.

It has been suggested that the pancreatic polypeptide response to a meal is inhibited by truncal vagotomy but returns towards normal with time. We have examined this hypothesis by measuring the pancreatic polypeptide response to a meal in five dogs before and 1 and 6 months after truncal vagotomy. Pancreatic polypeptide responses to food were significantly inhibited (P less than 0.01) in both postoperative studies. However, comparison of the 1- and 6-month responses revealed a significant increase (P less than 0.05) in the magnitude of the second hour response from 2.3 +/- 1.5% of the preoperative response at 1 month to 21.3 +/- 9.6% at 6 months. The pancreatic content of pancreatic polypeptide in four vagotomized dogs (1.06 +/- 0.06 nmol/g) was not significantly different from normal (1.30 +/- 0.33 nmol/g). These studies have shown that truncal vagotomy permanently inhibits the early phase of pancreatic polypeptide release but that the magnitude of the late phase response increases with time. Whether the response would ever return to that observed before vagotomy is uncertain.

Animals↗

Morphology of gel state phosphatidylethanolamine and phosphatidylcholine liposomes: a negative stain electron microscopic study.

The capture volumes (internal aqueous spaces) of liposomes prepared from a series of saturated phosphatidylcholines (PC) and saturated phosphatidylethanolamines (PE) had previously been found to be a function of lipid structure. PE vesicles have larger internal aqueous spaces than PC vesicles and for lipids with the same head group, capture volume increases with lengthening of the fatty acyl chains. Capture volume is determined by vesicle size, number of lamellae, and interlamellar distance. In this study, liposomes were found from a saturated PC or PE and their morphology studied In the gel state using the technique of negative staining transmission electron microscopy. The measured interlamellar distances were quite similar among these various lipids while the number of lamellae was found to decrease as the fatty acyl chain length increased. In general PEs form fewer lamellae than PCs and in particular mono- and di-methylated dipalmitoyl-PE form only unilamellar vesicles. The number of lamellae then appears to bear a relationship to the size of the capture volume in that liposomes with larger capture volumes have fewer lamellae.

Chemical Phenomena↗

Permeability of bilayers composed of mixtures of saturated phospholipids.

Liposomes composed of an equimolar binary mixture of phospholipids were from a series of saturated phosphatidylcholines (PC) and phosphatidylethanolamines (PE). Mixtures were chosen such that the two phospholipids differed either in terms of head group alone, chain length alone, or both head group and chain length. Cation effluxes, both with and without ionophores (nigericin and valinomycin) were measured over a range of temperatures that encompassed the regions of phase separation for these different lipid mixtures. There was a good correlation between the temperatures at which permeability maxima and phase separation occur. For phospholipid mixtures with the same acyl chain but different head groups (PC vs. PE), the PC component 'controls' permeability. For mixtures of PCs differing in chain length, the short chain lipid dominates the permeability pattern particularly if the chain length are sufficiently different. Lipids differing in both head group and chain length give rise to more complex permeability patterns. The results of the present study are interpreted in terms of a model in which one of the lipid components of the mixture may specifically congregate at defects between co-existing phases and thus 'regulate' permeability.

Liposomes↗

Morphology and position of growth cones in the developing Xenopus spinal cord.

Axonal growth cones in longitudinal fiber tracts of the developing spinal cord of Xenopus were examined using electron microscopy. Fiber tracts of the spinal cord develop by the ingrowth of fibers, into pre-existing longitudinally oriented spaces between adjacent neuroepithelial cells of the neural tube. Growth cones seen among the neurites of the tracts were identified by their generally larger size (1.2 X 4.5 micrometer), bulbous and irregular outlines, and cytoplasmic components. Overall cytoplasmic density was usually less than that of surrounding neuroepithelial cells and axons. They contained few organelles, among them assorted clear and densecored vesicles, agranular reticulum, and occasional mitochondria and autographic vacuoles. Microtubules were rarely present. Growth cones appeared to conform in outline to the space which they occupied. Smaller extensions which resembled the filopodia described by others insinuated themselves among other elements of the fiber fascicles. The filopodia contained a fine granular or filamentous feltwork. Growth cones consistently appeared at the interface of other axons in the fascicle and the peripheral neuroepithelial endfeet. In longitudinal sections of fascicles containing more than one growth cone, the growth cones were layered in a pattern suggesting that new cones are added by pushing between the next youngest fibers and the peripheral neuroepithelial processes of the cord. The possible significance of this finding in the achievement of order in the spinal tracts is discussed.

Animals↗

Airway resistance during esophageal phonation.

Prosthesis airway resistance calculations were completed for five Blom-Singer prostheses and esophageal source airway resistance estimates were made of five laryngectomized patients using the Singer-Blom voice restoration method. Airway resistance of the Blom-Singer prostheses ranged from 46 to 121 cmH20/LPS, while source airway resistance in these-subjects ranged from about 155 to 270 cmH20/LPS. These results revealed that the opposition of the voicing sources used in esophageal speech production to airflow through them is substantial and larger than that established for the normal, laryngeal source. Findings are interpreted to highlight major advantages the Singer-Blom (1980) method of speech/voice restoration has over esophageal speech/voice produced on a conventional basis and to reveal specific reasons for the failure of many laryngectomized patients to develop consistent voice and functionally serviceable speech.

Airway Resistance↗

Effect of beta-adrenergic blockers on the sickling phenomenon.

Dichloroisoproterenol (DCI) and propranolol were found to inhibit sickling in vivo when they were added to red-cell suspensions prior to deoxygenation. The effectiveness was maximal between PO2's of 30 and 40 mmHg (1 mmHg = 133.322 Pa). When cells were sickled at a low oxygen tension (PO2 = 32 mmHg), and then DCI was added later, the drug decreased the degree of sickling while the suspension was maintained at the same oxygen tension. The antisickling effect of these drugs was not antagonized by isoproterenol, a beta-adrenergic stimulator, by the addition of cAMP or increase of the intracellular calcium concentration. Other beta-blockers, such as MJ1999 (sotalol) and timolol, did not show antisickling activity. It was also found that DCI, propranolol, and timolol had some effect on the delay time of gelation of sickle-cell hemoglobin (Hb S), as well as on the oxygen affinity of sickle cells.

Adrenergic beta-Antagonists↗

Buspirone and diazepam in anxiety: a controlled study.

The anxiolytic properties of buspirone were assessed in a 4-week double-blind study in 240 anxious patients, 81 of whom received buspirone, 81 diazepam, and 78 placebo. Patients were required to have scores greater than or equal to 9 on the Covi and greater than or equal to 18 on the Hamilton Rating Scale for Anxiety, and to endorse at least 5 items on a 17-item Anxiety Entry Checklist. Among 212 evaluable patients, those who improved most were married, well-educated females who had both a positive family adjustment and a low level of depression. Diazepam produced relatively equal improvement in females and males. Diazepam seems more effective in reducing somatic symptoms, while buspirone appears more effective in reducing symptoms associated with cognitive and interpersonal problems. Main differences between the drugs were seen in side effect profiles.

Adult↗

Possible use of non-neuroleptic isomers of anti-psychotics in anti-sickling therapy.

Non-neuroleptic isomers and derivatives of three types of anti-psychotic drugs (phenothiazine, thioxanthene and benzocycloheptapyridoisoquinoline) were found to have in vitro anti-sickling activity. The anti-sickling activity of non-neuroleptic isomers is of the same magnitude as that of the anti-psychotic forms. The degree of the suppression of sickling ranged from 40-60% at a concentration of 200 microM. For these drugs, a significant correlation was found between the anti-sickling activity and the inhibition of calmodulin-stimulated phosphodiesterase activity. A possibility is raised that deoxy hemoglobin S polymerization is influenced by membrane-linked mechanisms.

Anemia, Sickle Cell↗

An ultrastructural examination of early ventral root formation in amphibia.

The morphology of early interactions between neural tube and myotome in the amphibian embryo and tail regenerate was examined using the electron microscope. Two types of contacts were observed. At the most primitive level where the myotome was yet unsegmented, multiple adhesive-type contacts linked neural tube and myotome. In newly segmented areas early ventral roots were recognizable as small bundles of one to five axons extending the short distance to the myotome. There was only one bundle per segment and in addition to axons, each bundle always contained one or more primitive glial cell processes which accompanied axons as they left the cord. At points of root exit primitive glial processes appeared to funnel axons into the root. The cytoarchitecture of the cord and the new roots suggested that the primitive glia may play a role in pathfinding for motor axons as they leave the cord and extend toward their targets.

Animals↗