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Biomedical subjects

F M Kendall

Publications and source records attributed to F M Kendall.

At least 19 recordsLinked to original sources

Gastrointestinal hormones and the quantitation of spontaneous duodenal motor activity.

This is a survey of the results of recent investigations on gastrointestinal (GI) peptide hormones. In addition to the classical GI hormones (secretin, gastrin, and cholecystokinin-pancreozymin (CCK-PZ], there are at least nine other peptides whose structures and GI effects are known. These include vasoactive intestinal polypeptide (VIP), gastric inhibitory polypeptide (GIP), motilin, pancreatic polypeptide (PP), substance P, neurotensin, somatostatin, enkephalins, and a bombesin-like gastrin-releasing peptide. It is now obvious that the traditional distinctions between hormones, neurotransmitters, and paracrines are rapidly becoming obsolete, as the actions and interactions of these substances within the complex motor system of the GI tract are gradually revealed. The study of perturbed states and toxic effects on the motor function of the small intestine is complicated by the integration of the activity of the small intestine with the activities of the body as a whole. A contemporary approach for evaluating intestinal contractile activity is described that uses computer assistance to measure the intercontractile interval (ICI). This technique may prove useful in assessing the effects of toxicological agents on spontaneous intestinal motor activity in vitro when the agents are delivered to the target sites by physiological mechanisms, in contrast to adding them to the tissue bath.

Animals↗

Three-dimensional intranuclear DNA organization in situ: three states of condensation and their redistribution as a function of nuclear size near the G1-S border in HeLa S-3 cells.

Characteristic variations in nuclear morphology occurring with variations in the physiological state of the cell have been observed in a number of systems to date. In this paper, we have critically examined the relationship between nuclear morphology and intranuclear DNA organization near the G1-S transition in HeLa S-3 cells, by the study of both the spatial distribution of optical density values and the optical density histograms for individual Feulgen-stained nuclei. Our results demonstrate that the majority of the DNA is located in a narrow shell surrounding the nuclear and nucleolar borders, and present evidence for at least three discrete states of chromatin condensation. Greater than 90% of the genome appears distributed among the two classes with larger density, and a redistribution between these two classes occurs as a function of changing nuclear size. Numerical simulations indicate that the observed distribution does not arise as an artifact related to overlapping but, in fact, actually represents discrete states of condensation. Interestingly, the extrapolated nuclear area at which the fraction of DNA in the state of highest density is reduced to zero, corresponds closely to the nuclear size shown elsewhere as representing the critical size that HeLa S-3 nuclei must exceed in order to initiate S phase.

Cell Nucleus↗

Reversible (G0) and nonreadily reversible (Q) noncycling cells in human peripheral blood. Immunological, structural, and biological characterization.

PHA-stimulated human lymphocytes (normal-resting-proliferating) at 0, 24, 48, 72, and 144 h were studied with Acridine Orange (AO) staining. By viable cell sorting, by subsequent subculturing, and by the use of biochemical, biophysical, and immunological assays, not only have the G0 resting and G1 (cycling) cell cycle phases been objectively characterized, but a separate subpopulation of quiescent cells that are functionally viable and deeply committed to nonproliferation, the Q cells, has been identified. Multiparameter cytofluorimetric analysis, methyl14C-thymidine incorporation, automated image analysis, and mitogen stimulation studies have shown that the "Q" cell, compared to the "G0" resting but easily recruitable cell, exhibits quite lower red and green AO emission, possesses 2c to 4c DNA content (rather than only 2c), has a higher average optical density, and is either nonrecruitable or recruitable-with-difficulty in PHA-stimulated lymphocyte cultures.

Acridine Orange↗

The quinternary chromatin-DNA structure. Three-dimensional reconstruction and functional significance.

Nuclear DNA-space images from Feulgen-stained HeLa cells synchronized at 1, 3, 5, 8, 12, 15, and 18 h following mitosis are digitized and their densitometric-geometric patterns are analyzed by means of a Quantimet 720-D image analyzer on line with a PDP11/40 computer. Frequency distributions of picture point optical densities for the phases and subphases as seen in nuclear images show that DNA packing changes are evident by means of ordinary optical microscopy. Radii of gyration of the images, and optical density profiles and distributions for several squashes of similar cells reveal that in particular instances chromatin DNA is distributed mostly towards the periphery, and usually with high circular isotropy. Cross power spectra of individual scan lines suggest that existence of higher order "quinternary" periodic structure for chromatin that modulates during the cell cycle. Three-dimensional reconstruction 2- micrometer sections of intact, Feulgen-stained mammalian tumor tissue show stainable material only toward the nuclear perimeter and not in the center (compatible with the evidence that initial thymidine incorporation in HeLa cells is generally at the nuclear border). Densitometric properties of reconstructed interphase chromatin-DNA bodies are highly coupled with similar properties of the whole nucleus, showing that a more condensed nucleus is always accompanied by a more condensed interphase chromatin DNA. The effect of micrococcal nuclease digestion on the digitized nuclear images is also presented. All the above data are then discussed in terms of a quinternary chromatin-DNA structure and its modulation during the cell cycle.

Cell Cycle↗

Coupling of nuclear morphometry to cell geometry and growth in human fibroblasts.

The nuclear morphology of WI-38 cells plated on increasing thicknesses of the polymer, poly-2-hydroxyethylmethacrylate, was studied. Changes in nuclear morphometry were found to parallel changes in cellular morphometry: namely a transition to a more rounded and compact conformation, with increasing thicknesses of the polymer. Such changes in nuclear morphometry were opposite to those already observed after stimulation of proliferation by serum addition and similar to those observed with increasing confluency. These results suggest that coupling between cell and nuclear geometry may represent a mechanism for the control of proliferation by cell shape in nontransformed cells.

Cell Division↗

Metabolic performance and GI function in magnesium-deficient rats.

A quantitative evaluation of the mass balance and GI motor effects of dietary magnesium deficiency in the adult male Sprague-Dawley rat is described. Seventy-seven animals were used. Both sham control and experimental groups were maintained on a commercial stock laboratory diet ad libitum for 30 days, after which the experimental rats were switched for 30 days to magnesium-deficient diet ad libitum, containing a magnesium concentration of 16.2 ppm. Ten rats were used to determine the acetylcholine responsiveness of duodenal muscle segments in vitro. In all cases, the segments from the deficient rats were hyperresponsive to a fixed acetylcholine dose. Forty-six rats were used to determine the average intestinal transit rate, which increased significantly in 30-day magnesium-deficient rats. A final series employed 21 rats who were housed in individual metabolic cages. After 5 days on the deficient diet, the average daily fecal pellet counts and fecal weights were significantly reduced. It is concluded that chronic magnesium deficiency is associated with altered GI motor function in the adult male rat.

Animals↗

Species difference in GI motor response to somatostatin.

Acute experiments were performed on overnight fasted chloralose-urethan anesthetized dogs, cats, rabbits, and rats. Under these conditions, somatostatin practically abolished gastric contractions and decreased GI tonus in all species examined. The canine duodenum, jejunum, and ileum exhibited only a contractile response to somatostatin, whereas motor activities of the small intestines of the cat, rabbit, and rat were inhibited. In all instances and at all dosages, both the inhibitory and excitatory effects showed suggestions of tachyphylaxis. The data also indicate that excitatory or inhibitory effects were not dependent on the presence of long arc pathways. It is concluded that somatostatin exerts a direct stimulatory effect on the canine small intestine that is mediated by the muscularis mucosa.

Animals↗

Update on the toxicity of inhaled methyl methacrylate vapor.

The current threshold limit value (TLV) of 100 ppm for methyl methacrylate vapor was originally set because it was considered to be a value sufficiently low to preclude either systemic toxicological effects or discomfort from irritation in workers chronically exposed to the vapor. Shortly after this limit was proposed we became interested in evaluating the toxicological properties of methyl methacrylate vapor and, subsequently, of providing experimental data which would be useful in evaluating the adequacy of this TLV. The purpose of this article is to review some of the more relevant literature prior to 1976 which pertains to inhalation exposure and to summarize our more recent data which resulted from statistically designed studies employing acute and subchronic exposures to known concentrations of the vapor including the near-TLV value of 116 ppm.

Animals↗

Evidence of reflexive beta adrenergic motor stimulation in the canine stomach and small intestine.

Studies in our laboratory have confirmed the previous observations that adequate electrical stimulation of either the left or right central vagus nerves in the dog after bilateral vagectomy produces relaxation of the stomach and small intestine. On the other hand, central vagal stimuli delivered to dogs that were either chronically reserpinized or were premedicated with the alpha adrenolytic phenoxybenzamine resulted in increased segmenting activity of these two organs. These excitatory responses were abolished by bilateral section of the sympathetic chains and could be reproduced by electrically stimulating the chains. The excitatory effects of either central vagal stimulation, peripheral sympathetic stimulation or intravenous isoproterenol administration could be abolished by dichloroisoproterenol. It was also determined that isoproterenol produced a tonic contraction of the separated muscularis mucosa which was distinguishable from a relaxation of the muscularis externa. It is suggested that a sympathetic pathway exists which is excitatory to the stomach and small intestine and that these excitatory effects are mediated by beta adrenergic neurotransmitters. The results further suggests that the beta excitatory reflex response is mediated by the muscularis mucosa as the target effector system.

Animals↗