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Biomedical subjects

J F Morris

Publications and source records attributed to J F Morris.

At least 163 records · Page 9Linked to original sources

Pancreatic glucagon in human foetal stomach.

A combination of immunocytochemistry at light and electron microscopic levels, direct radioimmunoassay and measurement after gel chromatography have been used to identify and characterise a glucagon-like peptide detected in human foetal stomach. Immunocytochemistry, with region specific antisera, demonstrated that the glucagon-containing cells were indistinguishable from pancreatic A cells. Radioimmunoassay of tissue extracts confirmed the presence of significant quantities of glucagon, mean 21 pmol/g wet weight (range 14-29) in 16-26 week old foetuses, increasing to 41 pmol/g wet weight (range 31-52) in 33-30 week old foetuses and after gel chromatography the peptide was found to elute at the same position as standard porcine glucagon. It is apparent, therefore, that the human foetal fundus contains significant quantities of true pancreatic-type glucagon.

Female↗

Membrane retrieval by vacuoles after exocytosis in the neural lobe of Brattleboro rats.

The possible role of microvesicles and vacuoles in the recapture of membrane after pituitary hormone release by exocytosis has been studied in homozygous Brattleboro rats. These mutant animals are unable to synthesize vasopressin and exhibit a steady state hypersecretion of oxytocin from the neural lobe as a result of the osmotic imbalance caused by their diabetes insipidus. This can be converted to a second steady state which approximates to the rate of secretion found in normal Long Evans rats by the administration of exogenous vasopressin daily for 30 days. In the Brattleboro rat, presumptive oxytocinergic nerve endings contain typical 160-170 nm diameter neurosecretory granules; other magnocellular nerve endings contain a population of smaller (approximately 100 nm diameter) dense-cored granules. The number of dense-cored granules was reduced in both types of nerve ending in the hypersecreting Brattleboro rats, but increased as a result of vasopressin treatment to levels which, for the classical neurosecretory granules, approximated that found in Long Evans rats. The microvesicle population of the nerve endings was essentially similar in quantitative terms in all the three groups (i.e. hypersecreting Brattleboro rats; vasopressin-treated Brattleboro rats and Long Evans controls). The number of vacuoles, on the other hand, was increased in nerve endings in the hypersecreting animals but reduced to levels found in Long Evans rats in the Brattleboro animals treated with vasopressin. Furthermore, the size of the vacuoles was comparable to the size of the dense-cored granules contained in the nerve endings. These changes in the vacuole population are exactly those that would be predicted for an organelle responsible for recapture of the granule membrane. We therefore conclude that membrane retrieval after exocytosis of neurosecretory granules in the neural lobe is achieved by vacuoles and that these organelles probably retrieve the membrane of the granule intact.

Animals↗

The effect of cimetidine on basal gastric acid secretion in the rat.

1. The effect of cimetidine on the basal gastric acid secretion of the rat has been investigated in an anaesthetized lumen-perfused preparation. 2. Six rats previously given large doses of cimetidine orally showed no significant difference in basal gastric acid secretion when compared with six control rats. 3. Intravenous administration of 1 mg and 8 mg of cimetidine failed to inhibit significantly basal gastric acid secretion. 4. Although rats with a basal gastric acid secretion above 2.5 micro Eq/10 min. showed a consistent small reduction in basal gastric acid secretion after intravenous cimetidine, this was not seen in rats with a basal gastric acid secretion below 2.5 micro Eq/10 min. 5. THese results contrast sharply with the pronounced inhibition of basal gastric acid secretion by cimetidine in man and the possible reasons for this are discussed. 6. The results are also contrasted with previous work on gastric fistula rats which showed higher basal gastric acid secretion and significant inhibition by cimetidine.

Administration, Oral↗

Characterization of the pituitary gonadotroph cells of hypogonadal (hpg) male mice: comparison with normal mice.

Hypogonadal (hpg) mice lack hypothalamic luteinizing hormone releasing hormone (LH-RH). Gonadotrophs from male hpg mice have been identified by immunocytochemistry for LH and quantitative electron microscopy allied with radioimmunoassay of the gonadotrophins. In comparison with those of normal mice, gonadotrophs in male hpg animals are less numerous and smaller, with less cytoplasm and rough endoplasmic reticulum and a smaller Golgi apparatus. They have fewer granules, especially those of larger (greater than 210 nm) diameter. Thus, in the absence of LH-RH, gonadotrophs can differentiate but remain relatively inactive.

Animals↗

Effects of luteinizing hormone releasing hormone on the gonadotrophs of hypogonadal (hpg) mice.

Hypogonadal (hpg) mice lack hypothalamic luteinizing hormone releasing hormone (LH-RH); consequently the pituitary gonadotrophs, though differentiated, remain inactive. The acute and chronic responses of gonadotrophs in hpg mice to LH-RH to male hpg mice produced an eightfold increase in plasma LH after 5 min, but granule depletion was not detectable ultrastructurally. Vacuoles (300-600 nm) were present more frequently in gonadotrophs from hpg mice given LH-RH compared with control mice. Daily s.c. administration of 2 micrograms LH-RH to male hpg mice for 20 days stimulated a 63-fold increase in the pituitary content of FSH but only a twofold increase in the pituitary content of LH. Testicular weight increased fivefold but the weight of the seminal vesicles did not change. The frequency of cells immunoreactive for LH increased (x 1.6), the gonadotrophs hypertrophied (x 1.9) and the cell content of granules increased (x 2.3) to values close to the normal range. The rough endoplasmic reticulum and Golgi apparatus became more prominent. A striking result of long-term daily administration of LH-RH was the accumulation of large (1-2 micrometers) lipid droplets in about 40% of gonadotrophs. All these changes induced by LH-RH regressed towards the untreated hpg state when LH-RH administration wad discontinued for 5 and 10 days. These results show that the gonadotrophs of hpg mice can be stimulated trophically by LH-RH, and that long-term administration stimulates the synthesis and release of the gonadotrophins but the effect on FSH is much greater than on LH.

Animals↗

Small-cell carcinoma of the lung--survival according to histologic subtype: a Veterans Administration Lung Group Study.

Six-hundred-twenty cases of small-cell carcinoma of the lung entered into the Veterans Administration Lung Group protocols 9-15 were retrospectively subdivided into histologic subtype, as proposed by the WHO (1977). Medium survival was greater for subtype No. 21 (lymphocyte-like) than for subtype No. 22 (intermediate) (17.2 vs. 12.6 weeks; P = .005). Patients with extensive disease survived longer with subtype No. 21 than subtype No. 22 (14.5 vs. 10.9 weeks; P = .026). However, no median survival difference was seen with limited disease. Survival for subtype 21 was greater than No. 22 (P = .016) for patients with poor initial performance status (IPS; Karnofsky 70 or less); for ambulatory patients (IPS 80-100) a survival advantage was seen for subtype No. 21 compared with No. 22, but did not quite reach statistical significance (P = .09). Survival in subtype No. 21 was better than in subtype No. 22 (24.3 vs. 14.7 weeks; P = .001) when no weight loss (less than 10 pounds over the six-month period prior to therapy) was documented. However, with weight loss (greater than 10 pounds) survival in each subtype was similar.

Body Weight↗

A mutation affecting L-serine and energy metabolism in E. coli K12.

The effects of a pleiotropic mutation ssd are described. This mutation results in decreased efficiency in the use of glucose and fructose as carbon source, inability to use succinate or to grow anaerobically, an alteration in the activity of enzymes responsible for the synthesis and degradation of L-serine, increased resistance to certain antibiotics, and a deficiency in proline transport. This mutation resembles various previously described mutations thought to affect' energy coupling factor' and is located in the same region of the chromosome. While the gene product affected by this mutation is still unidentified, it is clear that L-serine metabolism cannot be understood merely in terms of providing L-serine and its derivatives.

Anaerobiosis↗

Bronchoscopy and bone marrow examinations. An efficient strategy to establish the diagnosis of small cell carcinoma of the lung.

The utility of various diagnostic procedures, including fiberoptic bronchoscopy and bone marrow aspirate/biopsy for small cell carcinoma, was examined in 150 patients. From a chart review of the first 100 patients, 55 required an invasive procedure such as mediastinoscopy or thoracotomy to establish the tissue diagnosis. In 50 consecutive prospective patients, only four required an invasive procedure for tissue confirmation. Eighteen of the 50 prospective patients had positive iliac crest bone marrow aspirates or biopsies diagnostic for small cell carcinoma. Fiberoptic bronchoscopy was nondiagnostic in 15 prospective patients, but the bone marrow examination was diagnostic in 12 of this subgroup. The combination of fiberoptic bronchoscopy and bone marrow examination in patients with centrally located small cell carcinoma greatly reduced the need for more expensive and invasive diagnostic procedures.

Adult↗

Calcium localization in the rat neurohypophysis.

Neurosecretory nerve endings in the rat neurohypophysis release their hormones by exocytosis subsequent to an influx of calcium from the external medium. The nerve endings are characterized by the presence of neurosecretory granules, mitochondria, occasional vacuoles, and a population of microvesicles similar in appearance to spherical synaptic vesicles. The function of the microvesicles has, for a long time, been uncertain. In view of evidence that coated microvesicles isolated from cerebral cortex are capable of ATP-dependent calcium accumulation, a method has now been developed for the visualization of calcium in the neurohypophysis at the ultrastructural level. With this technique, calcium precipitates are consistently seen in the microvesicles, mitochondria and glial cell (pituicyte) nuclei. In addition, the pituicyte cytoplasm and perivascular space show a diffuse precipitate which can be removed by washing the tissue prior to fixation. The function of the microvesicles might therefore be to sequester calcium within the nerve endings.

Animals↗

Spirometric "abnormality" in a normal male reference population: further analysis of the 1971 Oregon survey.

Conventional criteria for spirometric impairment (FVC and FEV1 less than or equal to 79% predicted, FEF25-75 less than or equal to 74% predicted, FEV1/FVC less than or equal to 0.69 for most ages) were applied to 507 healthy nonsmoking male subjects in the 1971 Oregon survey. Frequency of air flow impairment was higher than expected for a normal population. Of all subjects, 17.8% had an "abnormal" FEF25-75% and 19.7% an "abnormal" FEV1/FVC. "Decreased" lung volumes were seen in older subjects; of those over 55 years of age, 8.8% had a reduced FVC and 11.8% a reduced FEV1. These rates in a normal population may be used as a rough baseline for making inferences about a population under study. Similar rates were found in a cross-sectional survey of nonsmoking males representative of the population of a large industrial state. The major reason for these high rates of "abnormal" spirometry lies in the conventional definitions of abnormality. Tables showing cut-off points for abnormal spirometric values based on a 95% confidence interval for adult males of all ages and heights permit an alternative method for classification as abnormal.

Adolescent↗

Depletion of neurosecretory granules and membrane retrieval in the sinus gland of the crab.

Ultrastructural aspects of hormone release from the sinus gland of the crab Carcinus maenas, have been studied by incubation of glands in vitro (i) in high potassium-containing media to induce hormone release; (ii) in a high potassium-containing calcium-free medium in which depolarisation but no hormone release would be expected; and (iii) in control saline. Uptake of horseradish peroxidase into subcellular organelles was also studied. Many neurosecretory granules could be found in the nerve terminals but, in contrast to mammalian neurosecretory systems, structures resembling microvesicles were extremely scarce. High potassium stimulation in the presence of calcium caused an 18% loss of granules from the nerve terminals associated with images of single and multiple exocytosis. It further caused an increase in vacuoles which could have accounted fro 33% of the membrane of the granules exocytosed. After incubation in high potassium-containing, calcium-free media there was no evidence either of exocytosis of granules or of an increase in the vacuole population. The population of sparse microvesicle-like structures was not significantly altered by incubation in either high potassium medium. Horseradish peroxidase reaction product could be found only in vacuoles of tissues stimulated by high potassium concentrations in the presence of calcium. It is concluded that this depolarising stimulus produces, in the presence of calcium, the release by exocytosis of about one sixth of all the granules in the sinus gland, and that vacuoles are the organelle responsible for the recapture of membrane after the exocytosis.

Animals↗

Map location of the ssd mutation in Escherichia coli K-12.

A pleiotropic mutation at the ssd locus was mapped at 86 min near rha. A mutation at the ssd locus resulted in elevated L-serine deaminase activity, inability to grow with succinate as the carbon source, and inability to grow anaerobic conditions.

Chromosome Mapping↗

Gastrin and the ultrastructure of G cells in the fasting rat.

The effect of fasting on serum and antral gastrin concentrations and G cell ultrastructure in the rat has been examined using a radioimmunoassay and quantitative electron microscopy. Serum gastrin levels in fasting animals were markedly reduced and there was also a significant decrease in antral gastrin concentrations after 48 hours and 72 hours of fasting. This was associated with a significant fall in the granule content and cytloplasmic volume of individual G cells, at its greatest by 48 hours. A relative absence of electron dense granules in the Golgi zones of cells from animals fasted for 72 hours suggested a paucity of newly formed granules, but fasting produced no detectable change in the electron density of the granule population taken as a whole. The results indicate that, during fasting, release and then synthesis of gastrin is inhibited, so that granule stores and cell size diminish. The correlation between the granule content of G cells and the antral content of gastrin suggests that hormone release occurs by exocytosis, rather than by any change in the content of individual granules.

Animals↗

Gastrin and the ultrastructure of G cells after stimulation with acetylcholine.

The effect of intragastric administration of acetylcholine on serum and antral gastrin concentrations of rats has been examined using a radioimmunoassay and quantitative electron microscopy. Exposure of the stomach of rats, previously fasted for 24h, to 2% acetylcholine for either 0.5 or 2h resulted in a significant 4--5 fold increase in serum gastrin concentrations to levels similar to those found in fed animals. Such treatment produced no detectable change in antral gastrin concentration or in the number or electron density of secretory granules in the G cells. This lack of detectable change in the G cells was not unexpected since our calculations suggest that less than 10% of the total gastrin stored in the antrum is released over 2h as a result of the stimulation with acetylcholine. The proportion of electron-lucent secretory granules was, however, markedly increased by prolonged fixation in aldehydes. The increase was similar in both ACh stimulated and control animals. These results indicate that the ultrastructural appearance of G cell secretory granules in influenced far more by the conditions of fixation than by the release of gastrin. They therefore cast considerable doubt on the hypothesis that gastrin is released by molecular dispersion from the granules.

Acetylcholine↗

Factors influencing the in vivo stability of L-serine deaminase activity in E. coli K12.

L-Serine deaminase (L-SD) is unstable in intact cells of Escherichia coli K12. The extent of this instability is dependent on the nitrogen content of the medium in which the enzyme is synthesized, and on that in which it is tested. Enzyme activity in cells grown with an inorganic nitrogen source is unstable in the presence of inorganic nitrogen; enzyme activity in cells grown with an organic nitrogen source is unstable in the presence of the amino acids glycine and leucine.

Ammonium Sulfate↗