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Biomedical subjects

G Bennett

Publications and source records attributed to G Bennett.

At least 127 records · Page 7Linked to original sources

Influence of colchicine and vinblastine on the intracellular migration of secretory and membrane glycoproteins: II. Inhibition of secretion of thyroglobulin in rat thyroid follicular cells as visualized by radioautography after 3H-fucose injection.

Young (40 gm) rats were given a single intravenous injection of colchicine (4.0 mg) or vinblastine (2.0 mg). At 10 min after colchicine and 30 min after vinblastine administration, the rats were injected with 3H-fucose. Control rats received 3H-fucose only. All rats were sacrificed 90 min after 3H-fucose injection and their tissues processed for radioautography. In thyroid follicular cells of control animals, at this time interval, 57% of the total label was associated with colloid and secretory vesicles in the apical cytoplasm while 27% was localized in the Golgi apparatus and neighboring vesicles. In experimental animals, the proportion of label in colloid and apical vesicles was reduced by more than 69% after colchicine and more than 83% after vinblastine treatment. The proportion of label in the Golgi region, on the other hand, increased by more than 125% after colchicine and more than 179% after vinblastine treatment. Within the Golgi region, the great majority of the label was associated with secretory vesicles which accumulated adjacent to the trans face of the Golgi stacks. It is concluded that the drugs do not interfere with passage of newly synthesized thyroglobulin from the Golgi saccules to nearby secretory vesicles, but do inhibit intracellular migration of these vesicles to the cell apex. In most cells the number of vesicles in the apical cytoplasm diminished, but this was not always the case, suggesting that exocytosis may also be partially inhibited. The loss of microtubules in drug-treated cells suggests that the microtubules may be necessary for intracellular transport of thyroglobulin.

Animals↗

Influence of colchicine and vinblastine on the intracellular migration of secretory and membrane glycoproteins: III. Inhibition of intracellular migration of membrane glycoproteins in rat intestinal columnar cells and hepatocytes as visualized by light and electron-microscope radioautography after 3H-fucose injection.

In the first paper of this series (Bennett et al., 1984), light-microscope radioautographic studies showed that colchicine or vinblastine inhibited intracellular migration of glycoproteins out of the Golgi region in a variety of cell types. In the present work, the effects of these drugs on migration of membrane glycoproteins have been examined at the ultrastructural level in duodenal villous columnar cells and hepatocytes. Young (40 gm) rats were given a single intravenous injection of colchicine (4.0 mg) or vinblastine (2.0 mg). At 10 min after colchicine and 30 min after vinblastine administration, the rats were injected with 3H-fucose. Control rats received 3H-fucose only. All rats were sacrificed 90 min after 3H-fucose injection and their tissues processed for radioautography. In duodenal villous columnar cells, 3H-fucose labeling of the apical plasma membrane was reduced by 51% after colchicine and by 67% after vinblastine treatment; but there was little change in labeling of the lateral plasma membrane. Labeling of the Golgi apparatus increased. This suggests that labeled glycoproteins destined for the apical plasma membrane were inhibited from leaving the Golgi region, while migration to the lateral plasma membrane was not impaired. In hepatocytes, labeling of the sinusoidal plasma membrane was reduced by 83% after colchicine and by 85% after vinblastine treatment. Labeling of the lateral plasma membrane also decreased, although not so dramatically. Labeling of the Golgi apparatus and neighboring secretory vesicles increased. This indicates that the drugs inhibited migration of membrane glycoproteins from the Golgi region to the various portions of the plasma membrane. Accumulation of secretory vesicles at the sinusoidal front suggests that exocytosis may also have been partially inhibited. In both cell types, microtubules almost completely disappeared after drug treatment. Microtubules may, therefore, be necessary for intracellular transport of membrane glycoproteins, although the possibility of a direct action of these drugs on Golgi or plasma membranes must also be considered.

Animals↗

The cardiovascular effects of high-dose butorphanol-nitrous oxide anaesthesia before and during operation.

The cardiovascular effects of high doses of butorphanol (0.3-0.45 mg . kg-1) plus 60 per cent N2O anaesthesia were measured at unconsciousness, following tracheal intubation, and immediately before and at one and ten minutes after surgical stimulation in 17 A.S.A. class I and II patients undergoing elective gastric or gall bladder surgery. Butorphanol and N2O produced unconsciousness with only small decreases in heart rate and cardiac output but did not result in sufficient analgesia to block or treat stimulation of the cardiovascular system secondary to tracheal intubation or surgical incision, even when supplemented with additional butorphanol to high cumulative dose levels (1.0 mg . kg-1). The data suggest that even high dose butorphanol - N2O anaesthesia requires supplementation with other anaesthetics or anaesthetic adjuvants to prevent cardiovascular stimulation during general abdominal surgery.

Adjuvants, Anesthesia↗

Accumulation of [3H]fucose-labelled glycoproteins in the Golgi apparatus of dorsal root ganglion neurons during inhibition of fast axonal transport caused by exposure of the ganglion to Co2+-containing or Ca2+-free medium.

Previous in vitro studies have established that Co2+-containing or Ca2+-free media interfere with the initiation of the fast axonal transport of proteins. The present study has used light- and electron-microscope radioautography to compare the distribution of [3H]fucose-labelled glycoproteins in neuronal cell bodies of control dorsal root ganglia and ganglia incubated for 16-17 h in Ca2+-free medium or in medium containing 0.18 mM Co2+. The radioautographic reaction in control cell bodies was diffusely scattered throughout the cytoplasm; grain counts revealed that 22% of the reaction was associated with elements of the Golgi apparatus and 78% was over other organelles and the remainder of the cytoplasm. In most experimental cell bodies, 78% of the silver grains were clustered over elements of the Golgi complex whereas other organelles and the remainder of the cytoplasm were comparatively much less labelled; structural alterations of the Golgi apparatus were also produced by the modified media. In parallel studies where the radioactivity in nerve trunks and ganglia was measured by liquid scintillation counting, it was found that the Ca2+-free medium and the Co2+-containing medium both reduced by approximately 80% the quantity of [3H]fucose-labelled glycoproteins which were carried by the fast axonal transport system; they did so without interfering with the incorporation of [3H]fucose into glycoproteins. The results indicate that in the presence of Co2+ or in the absence of Ca2+ the proteins which are destined for fast axonal transport accumulate at the Golgi apparatus of neuronal cell bodies. These results thus suggest that Ca2+ is required for proteins to leave the Golgi region in transit to the fast axonal transport system.

Animals↗

Criminal identification comparison: aural versus visual identifications resulting from a simulated crime.

This research was undertaken to investigate and contrast visual and aural/perceptual identifications of a previously unknown individual from a set of photographic and tape-recorded exemplars following a simulated crime. All participants were volunteers for the "criminal," the victim of an "assault," and all suspects drawn from a Reserve Officer Training Corps (ROTC) class; the "witnesses" were 61 students in a law class. The student/witnesses were divided into four groups. Group A made three identifications (serially) one day, one week, and two weeks after the crime took place. Group B saw the photographs and heard the tapes only once a week after the incident, and Group C only after two weeks had elapsed. Witnesses in a fourth group (D) followed the same schedule as did Group A; however, they were presented with foils similar in appearance and speech to the criminal. Group D was presented both the foil and criminal in the photographic lineup at the final judging session. The results demonstrated that visual identification can be quite accurate although not consistently or predictably so. By contrast, aural/perceptual identifications were relatively poor. No strong trends for latencies were observed, either for repeated trials or for procedures involving different initiation latencies; nor did confidence levels appear to be related to accuracy of judgment. Finally, when a similar looking foil was included in the identification task, there was a weak trend for the foil to be chosen more often in subsequent trials. These results support the position that eyewitness--and especially earwitness--testimony should be viewed by judges and juries with greater caution than has been the case in the past; by appropriate instructions, juries should be given assistance in interpreting and in assigning appropriate weight to this kind of testimony.

Adult↗

Psychiatric disorders in civilian pilots.

Psychiatric disorders are second only to cardiovascular disorders as a cause of permanent loss of licence in both professional aircrew and private pilots in the UK. In professional aircrew, psychiatric disorders are commonly aviation-related, whilst in private pilots less effective selection and the stresses of business and personal affairs are common factors. Because human error is a major cause of accidents, the early diagnosis of disorders of thought and behaviour is clearly crucial in promoting flight safety. Airline doctors and AMEs must play the most important part.

Aerospace Medicine↗

Lack of autologous mixed lymphocyte reaction in patients with chronic lymphocytic leukemia: evidence for autoreactive T-cell dysfunction not correlated with phenotype, karyotype, or clinical status.

In the present study, there was a complete lack of autologous MLR between responding T cells or T subsets and unirradiated or irradiated leukemic B cells or monocytes in all 20 patients with CLL, regardless of disease status, stage, phenotype, or karyotype of the disease. The stimulating capacity of unirradiated CLL B cells and CLL monocytes or irradiated CLL B cells was significantly depressed as compared to that of respective normal B cells and monocytes in allogeneic MLR. The responding capacity of CLL T cells was also variably lower than that of normal T cells against unirradiated or irradiated normal allogeneic B cells and monocytes. The depressed allogeneic MLR between CLL B cells or CLL monocytes and normal T cells described in the present study could be explained on the basis of a defect in the stimulating antigens of leukemic B cells or monocytes. The decreased allogeneic MLR of CLL T cells might simply be explained by a defect in the responsiveness of T lymphocytes from patients with CLL. However, these speculations do not adequately explain the complete lack of autologous MLR in these patients. When irradiated CLL B cells or irradiated CLL T cells were cocultured with normal T cells and irradiated normal B cells, it was found that there was no suppressor cell activity of CLL B cells or CLL T cells on normal autologous MLR. Our data suggest that the absence or dysfunction of autoreactive T cells within the Tnon-gamma subset account for the lack of autologous MLR in patients with CLL. The possible significance of the autologous MLR, its relationship to in vivo immunoregulatory mechanisms, and the possible role of breakdown of autoimmunoregulation in the oncogenic process of certain lymphoproliferative and autoimmune diseases in man are discussed.

Adult↗

The site of incorporation of sialic acid residues into glycoproteins and the subsequent fates of these molecules in various rat and mouse cell types as shown by radioautography after injection of [3H]N-acetylmannosamine. I. Observations in hepatocytes.

To study the site of incorporation of sialic acid residues into glycoproteins in hepatocytes, we gave 40-g rats and 15-g Swiss albino mice a single intravenous injection of [3H]N-acetylmannosamine (8 mCi) and then sacrificed them after 2 and 10 min. To trace the subsequent migration of the labeled glycoproteins, we injected 40-g rats with 4 mCi of [3H]N-acetylmannosamine and sacrificed them after 20 and 30 min, 1, 4, and 24 h, and 3 and 9 d. Concurrent biochemical experiments were carried out to test the specificity of injected [3H]N-acetylmannosamine as a precursor for sialic acid residues of glycoproteins. In radioautographs from rats and mice sacrificed 10 min after injection, grain counts showed that over 69% of the silver grains occurred over the Golgi region. The majority of these grains were localized over the trans face of the Golgi stack, as well as over associated secretory vesicles and possibly GERL. In rats, the proportion of grains over the Golgi region decreased with time to 37% at 1 h, 11% at 4 h, and 6% at 24 h. Meanwhile, the proportion of grains over the plasma membrane increased from 4% at 10 min to 29% at 1 h and over 55% at 4 and 24 h; two-thirds of these grains lay over the sinusoidal membrane, and the remainder were equally divided over the lateral and bile canalicular membranes. Many silver grains also appeared over lysosomes at the 4- and 24-h time intervals, accounting for 15-17% of the total. At 3 and 9 d after injection, light microscope radioautographs revealed a grain distribution similar to that seen at 24 h, with a progressive decrease in the intensity of labeling such that by 9 d only a very light reaction remained. Because our biochemical findings indicated that [3H]N-acetylmannosamine is a fairly specific precursor for the sialic acid residues of glycoproteins (and perhaps glycolipids), the interpretation of these results is that sialic acid is incorporated into these molecules in the Golgi apparatus and that the latter then migrate to secretion products, to the plasma membrane, and to lysosomes in a process of continuous renewal. It is possible that some of the label seen in lysosomes at later time intervals may have been derived from the plasma membrane or from material arising outside the cells.

Animals↗

The site of incorporation of sialic acid residues into glycoproteins and the subsequent fates of these molecules in various rat and mouse cell types as shown by radioautography after injection of [3H]N-acetylmannosamine. II. Observations in tissues other than liver.

Biochemical evidence from the preceding paper indicated that [3H]N-acetylmannosamine may be used as a fairly specific precursor for the sialic acid residues of glycoproteins (and perhaps glycolipids) in radioautographs of rat liver and duodenum. In order to study the site of incorporation of this label in cell types of various tissues, we gave 40-g rats and 15-g Swiss albino mice a single intravenous injection of 8 mCi of [3H]N-acetylmannosamine and sacrificed them after 2 and 10 min. To trace the subsequent migration of the labeled glycoproteins, we injected 40-g rats with 4 mCi of [3H]N-acetylmannosamine and sacrificed them after 20 and 30 min, 1, 4, and 24 h, and 3 and 9 d. Light microscope radioautographic analysis revealed that in a great variety of cell types the label was initially localized to the Golgi region. Electron microscope radioautographic analysis of duodenal villous columnar and goblet cells, pancreatic acinar cells and Paneth cells, from rats and mice sacrificed 10 min after injection, showed that the silver grains were localized over Golgi saccules (and adjacent secretion granules). In kidney proximal and distal tubule cells reaction was initially localized to the Golgi apparatus in some areas of the kidney cortex whereas in other areas it was more diffuse. In all cells, the proportion of silver grains over the Golgi apparatus decreased with time after injection while an increasing number of grains appeared over secretion products in secretory cells or over the plasma membrane in other cell types. Lysosomes also became increasingly labeled at later time intervals. The above results suggest that in most cell types sialic acid residues are incorporated into glycoproteins (and perhaps glycolipids), primarily in the Golgi apparatus. With time, these newly synthesized molecules migrate to secretion products, to the plasma membrane, or to the lysosomes.

Animals↗

Malignant hyperthermia: current perspectives.

The incidence, etiology, clinical manifestations, and management of malignant hyperthermia (MH) are reviewed. The syndrome of MH is recognized as one of the causes of anesthesia-related deaths. It is considered pharmacogenetic because both an abnormal gene and precipitating environmental factors are necessary to produce an acute reaction. Metabolic defects, involving a derangement of calcium dynamics, appear to be the common characteristic of susceptible individuals. Calcium release and uptake from the sarcoplasmic reticulum is altered when an individual with MH is exposed to certain anesthetic agents or triggering physical and emotional stresses. Muscle rigidity, tachycardia, tachypnea, and high fever can lead to other complications and death. Management of an acute reaction of MH includes cooling methods to lower body temperature, hyperventilation, sodium bicarbonate control of acidosis, maintenance of fluid and electrolyte balance, and the administration of dantrolene sodium. A thorough family history, baseline CPKs, caffeine-halothane contracture tests, and ultramicroscopic examination of muscle biopsy specimens are recommended as screening techniques. The early administration of dantrolene sodium in acute reaction of MH has been shown to rapidly alleviate the symptoms and ensuing severe complications. Individuals with a strong family history of MH or previous episodes may be treated with oral dantrolene sodium before surgery to effectively prevent a crisis, and after surgery to prevent recurrence.

Creatine Kinase↗

Psycho-social aspects of chronic pain in spinal cord injury.

The relationship between persistent pain in spinal cord injury and medical-descriptive, demographic, psychological and familial-social data was studied. Multiple linear regression and discriminant analysis were used to predict (1) presence or absence of pain; (2) severity of pain; (3) time post-injury onset of pain; (4) whether or not pain interfered with activities of daily living. The best combinations of predictor variables accounted for only 15 and 19% of the dependent measures pain vs. no-pain and onset of pain, respectively. The best combinations of predictor variables accounted for 43 and 44%, respectively of the dependent measures severity of pain and whether or not pain interfered with activities of daily living. Higher levels of subjective pain were associated with greater age, higher verbal intelligence, higher levels of anxiety and a more negative psycho-social situation. Persons who reported pain interfering with activities of daily living were more likely to be older, of higher intelligence, more depressed, clinically rated as experiencing greater levels of distress and immersed in a more negative psycho-social environment. The importance of psycho-social variables in the understanding of persistent spinal cord injury pain and the need for prospective studies along these lines are demonstrated.

Activities of Daily Living↗

Prostacyclin: a solution to some problems of extracorporeal circulation. Experiments in greyhounds.

In cardiopulmonary-bypass experiments in greyhounds the effects of adding prostacyclin, prostacyclin plus heparin, and heparin alone to the extracorporeal circulation were compared. With heparin alone platelet count and function were reduced, the pressure differential across the arterial filters rose, platelet deposits were found on the arterial filters, and plasma-fibrinogen levels fell. Plasma from these dogs was toxic to fetal-mouse hearts in culture. With prostacyclin alone, fibrinogen levels fell, but the platelets were preserved. With a combination of prostacyclin and heparin, platelet count and function were maintained, there was no consumption of fibrinogen, and there was little deposition on the arterial filters.

Animals↗