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Biomedical subjects

A Day

Publications and source records attributed to A Day.

At least 127 records · Page 7Linked to original sources

Normal tactile threshold in monkeys with neglect.

To learn whether animals with parietotemporal lesions have sensory inattention or defective intention, we trained monkeys to respond with the contralateral limb to a threshold tactile stimulus. After parietotemporal lesions that induced neglect, the monkeys continued to respond normally to threshold stimuli on the side opposite the lesion (the neglected side), but made errors when stimulated on the normal side (ipsilateral to the lesion), often failing to use the contralateral extremity. On this learned task, there was no abnormality of sensory input or sensory attention. The problem was attributed to an impaired preparation to respond (intention).

Animals↗

A two-step purification of ATP-citrate lyase from rat liver and its use in a fluorometric assay for N-acetylglutamate synthetase.

ATP-citrate lyase (EC 4.1.3.8) was purified to homogeneity from the liver of rats maintained on a diet containing no fat and high carbohydrate. The procedure involves two steps: dye-ligand chromatography on yellow MX-6G Sepharose CL-4B and ion-exchange chromatography on DEAE-Trisacryl. The specific activity of the enzyme was 10 mumol X min-1 X mg-1 at 25 degrees C, which is equal to the highest specific activity reported to date. The yield was also the highest reported to date, being in excess of 50%, and the enzyme isolated by this procedure has little proteolytic nicking. The pure enzyme was used to establish a coupled fluorometric assay for N-acetylglutamate synthetase (amino-acid acetyltransferase, EC 2.3.1.1) based on coupling coenzyme A production to the oxidation of NADH via ATP-citrate lyase and malate dehydrogenase. The method is easy to perform compared with existing methods and enables the measurement of 100 pmol X min-1 of N-acetylglutamate synthetase activity. The method is generally applicable for measurement of enzymes which produce coenzyme A. The fluorometric method was used to measure the Km for glutamate and acetyl coenzyme A at pH 7.0 and 25 degrees C, which were 8.2 and 0.4 mM, respectively. Arginine at 1 microM gave half-maximal activation of N-acetylglutamate synthetase.

ATP Citrate (pro-S)-Lyase↗

Phase II trial of VP-16-213 in advanced ovarian carcinoma.

We have reevaluated the effectiveness of VP-16-213 in advanced ovarian carcinoma. Twenty-five patients with measurable disease were treated for 3 days every 2 weeks with an escalating dose of the oral preparation. Twenty-two percent of 23 evaluable patients responded including one complete response. The median duration of response was 20 weeks and median survival 32 weeks. Toxicity was mild. The response rate observed is relatively high in patients pretreated with cis-platinum. VP-16-213 deserves further study, especially in combination with cis-platinum.

Administration, Oral↗

A comparison of intravaginal PGF2 alpha and intravenous oxytocin to stimulate labour after membrane rupture.

A prospective randomized controlled trial of 202 patients was set up to examine the efficiency and safety of 40 mg of intravaginal prostaglandin F2 alpha (PGF2 alpha) in a tylose gel to stimulate labour after artificial or spontaneous membrane rupture. The control group received a standard intravenous oxytocin regimen. The PGF2 alpha treated group had a significantly shorter length of labour (6.2 +/- 3.6 hours) compared to the oxytocin group (7.5 +/- 4.3 hours) (p less than 0.05). The analgesic requirements were significantly reduced in the PGF2 alpha treated patients. In PGF2 alpha treated patients 46 of 105 required no analgesia whereas 17 of 97 oxytocin treated patients required no analgesia (p less than 0.001). There were similar reductions for epidural (p less than 0.005) and pethidine requirements (p less than 0.005). No differences were found between groups with regards mode of delivery. There were no adverse maternal side-effects associated with PGF2 alpha usage. A significant reduction (p less than 0.05) in the incidence of neonatal jaundice requiring phototherapy occurred in the PGF2 alpha group. Prostaglandin F2 alpha appears to be a safe, efficient and better alternative to intravenous oxytocin to stimulate labour in the presence of ruptured membranes, allowing ambulation, a reduction in length of labour and less need for analgesia and intravenous therapy.

Anesthesia, Obstetrical↗

Failure of cholinergic blockade to prevent bronchodilatation following deep inspiration.

The role of the cholinergic system in the phenomenon of bronchodilatation following a deep inspiration (BDFI) in humans has not been well established, although animal studies have suggested the cholinergic system to be of prime importance. We therefore induced cholinergic blockade with inhaled ipratropium bromide (Sch-1000) in five asymptomatic subjects and then assessed whether BDFI had been abolished. Since BDFI is only evident where there is normal or increased bronchomotor tone, prostaglandin F2 alpha (PGF2 alpha), a noncholinergic bronchoconstrictor, was used to re-establish bronchomotor tone in the presence of cholinergic blockade. At each stage the presence or absence of BDFI was assessed by comparing flows from a partial forced expiratory maneuver started at approximately 60% of vital capacity (Vmaxp) with flows from a forced expiratory maneuver started at lung capacity (Vmaxc). Flows were measured at the last 40% of vital capacity. The percent ratio of Vmaxp/Vmaxc was used as an indicator of BDFI. In the presence of cholinergic blockade and with reestablishment of bronchomotor tone with PGF2 alpha, BDFI could still be demonstrated (Vmaxp/Vmaxc percent ratio: control 110.3 +/- 10.6, after Sch-1000 129.4 +/- 10.3, after Sch-1000 and PGF2 alpha 59.4 +/- 6.9; P = 0.001). We conclude that there is not an essential role for the cholinergic system in the phenomenon of BDFI in healthy individuals.

Adult↗

Hypertrophic pulmonary osteoarthropathy in four patients with interstitial pulmonary disease.

The association between digital clubbing and idiopathic pulmonary fibrosis has been well established; however, the simultaneous occurrence of hypertrophic pulmonary osteoarthropathy and interstitial fibrosis, in the absence of neoplastic disease, has only been described in two case reports and was not mentioned in any of 336 patients described in several recent reviews. Among 70 patients referred for investigation of pulmonary infiltrates, four were found to have hypertrophic pulmonary osteoarthropathy associated with interstitial pulmonary disease, in the absence of malignant disease. We conclude that the use of bone scans and roentgenographic examination of the extremities may draw attention to an association between hypertrophic pulmonary osteoarthropathy and idiopathic pulmonary fibrosis.

Aged↗

Chloroplast DNA deletions associated with wheat plants regenerated from pollen: possible basis for maternal inheritance of chloroplasts.

Albinism in plants regenerated from pollen by anther culture may result from the same mechanisms as postulated to be responsible for maternal inheritance of chloroplasts. Consistent with this view, Southern blotting was used to show that large regions of the chloroplast genome (over 80% in one case) were deleted in the major ctDNA molecules present in eight albino wheat plants regenerated from separate pollen calluses. A wide variety of deleted ctDNA molecules was present in these plants. Most albino plants appeared to contain a heterogeneous population of ctDNA molecules. Albino plant 6 contained one major type of deleted ctDNA molecule that had a circular 39 kb restriction map. The retention of only two Pst l (unaltered in size) fragments in albino plant 7 may delimit a region of ctDNA that contains a replication origin.

Base Sequence↗

Effects of cigarette smoking and short-term smoking cessation on airway responsiveness to inhaled methacholine.

Threshold of airway responsiveness to methacholine aerosol was determined in 53 apparently healthy persons. In 18 nonallergic nonsmokers matched according to sex and age to 18 nonallergic smokers, the mean methacholine threshold of airway response (T), as measured using partial flow-volume curves, had a tendency to be greater in nonsmokers, but the difference was not significant for the group as a whole; it was, however, significant for a subset of 9 matched pairs with a cigarette consumption greater than 10 pack-years (mean T nonsmokers, 2.8 mg/ml; smokers, 0.3; p = 0.036). In 17 smokers who stopped smoking for 99 days in average, T was not significantly different for the group as a whole, although the majority of the smokers reported improvement of respiratory symptoms after cessation of smoking. The results of this study indicate that cigarette smoking is associated with increased airways responsiveness to inhaled methacholine and that this effect is dose related.

Adult↗

Chronic ventilatory failure caused by abnormal respiratory pattern generation during sleep.

A 67-yr-old man presented with a 4-yr history of chronic ventilatory failure in the absence of any restrictive or obstructive ventilatory defect. Detailed neurologic investigations were unremarkable, and the response of minute volume of ventilation to inhaled CO2 was normal. During sleep there was no evidence of upper airway obstruction, and minute volume of ventilation averaged 6.7 L/min, compared with 7.2 L/min during quiet wakefulness. However, sleep was associated with a rapid and shallow pattern of breathing, resulting in high dead space ventilation, inadequate alveolar ventilation, hypoxemia, and hypercapnia. Correction of the abnormal ventilatory pattern during sleep by diaphragmatic pacing abolished all features of chronic respiratory failure. The findings indicate that a disorder of respiratory pattern during sleep can produce chronic ventilatory failure, despite normal respiratory drive.

Aged↗

Evaluation of the rat thyroid cell strain FRTL-5 as an in-vitro bioassay system for thyrotrophin.

The cyclic AMP response to bovine TSH was characterized in a strain of rat thyroid follicular cells ( FRTL -5) maintained in continuous culture. Significant stimulation of intracellular cyclic AMP was attained at a TSH dose of 5 muu./ml. Cyclic AMP accumulation continued to increase, at higher TSH doses, with no evidence for attainment of a maximum level at the highest dose tested (5 mu./ml). The precision of TSH measurement was better than 10% over the range 50-5000 muu./ml, comparing favourably with that observed with analogous assays based on human cells, tissue slices or membrane preparations. Using sequential subcultures of FRTL -5 cells, the between-assay variation in response to a single dose of a standard preparation of bovine TSH (53/11; 370 muu./ml) was of the order of 20% which compared favourably with the between-assay variation observed with different cultures of human thyroid cells. Prolongation of the incubation of FRTL -5 cells with TSH to 3 h revealed a progressive increase in the extracellular accumulation of cyclic AMP. Addition of TSH to resting FRTL -5 cells resulted in a stimulation of inorganic iodide uptake with pronounced bell-shaped dose-response characteristics. Thus a maximum uptake was observed at a TSH dose of 100 muu./ml with a significant reduction at higher doses. Acute stimulation of cells with TSH (100 muu./ml) resulted in a rapid and marked alteration in cell morphology, with evidence of cellular retraction and surface ruffling.

Animals↗

Hysterectomy and psychiatric disorder: I. Levels of psychiatric morbidity before and after hysterectomy.

One hundred and fifty-six women with menorrhagia of benign origin were interviewed before hysterectomy, and re-interviewed six months post-operatively (n = 147), and again 18 months post-operatively (n = 148). Levels of psychiatric morbidity were significantly higher before the operation than after. On the Present State Examination, 58 per cent of patients were psychiatric cases before surgery, as against 29 per cent at the 18-month follow-up. Similar post-operative improvements were found on measures of mood (POMS), and of psychosexual and social functioning. Most of these improvements had occurred within three to six months after the operation. Both before and after hysterectomy, levels of psychiatric morbidity were high by comparison with women in the general population, but lower than in psychiatric patients. The pre-operative psychiatric morbidity had been mainly of long duration.

Adult↗

The node of Ranvier in early Wallerian degeneration: a freeze-fracture study.

Using the freeze-fracture technique, the sciatic nerve of the rat and rabbit was examined distally at 24 h after crush, with particular reference to the node of Ranvier and paranode. The paranodes, in the majority of myelinated fibres, showed a loss of the cytoplasmic circumferential bands and longitudinal columns and their associated membrane pores which characterise the normal Schwann cell surface. Axonal changes consisting of accumulations of axoplasmic organelles occurred at both the node and paranode. At the nodes large intramembraneous particles in the axolemma (E face) appeared unchanged. Nodal Schwann cell microvilli and paranodal myelin terminal loops were generally unaffected. The findings are discussed in terms of the decrease in amplitude of the action potential which occurs in early Wallerian degeneration.

Action Potentials↗

Schwann cell plasma membrane changes induced by nerve crush. A freeze-fracture study.

Twenty-four hours after nerve crush, the Schwann cell plasma membrane and subjacent outer layer of Schwann cell cytoplasm were examined by freeze-fracture in myelinated fibres from the rat and rabbit sciatic nerves. The irregular circumferential bands and longitudinal columns of cytoplasm which characterise the surface of the normal Schwann cell were diminished or had disappeared. Concomitantly, the membrane pores (of micropinocytotic vesicles or caveolae) which are normally present on the bands and columns were also lost. The loss of these specialised features is discussed in terms of the onset of cell dedifferentiation in association with cell division. The Schwann cell plasma membrane acquired a new feature: deep impressions of adjacent collagen fibres, present particularly on the cytoplasmic bands and columns and presumed to be related to a transient increase in fibre diameter.

Animals↗

Enzymic assays for isomers of 2,6-diaminopimelic acid in walls of Bacillus cereus and Bacillus megaterium.

An enzymic assay for individual isomers (meso-, LL- and DD-) of 2,6-diaminopimelate was developed. The enzyme 2,6-diaminopimelate decarboxylase specifically attacked meso-diaminopimelate and was used to measure this isomer manometrically. The meso- and LL-isomers were measured together manometrically in a coupled assay with diaminopimelate decarboxylase and diaminopimelate epimerase (which converts LL-diaminopimelate into meso-diaminopimelate). The DD-isomer was not attacked by either enzyme and was measured, as residual diaminopimelate after the coupled assay, by a colorimetric method, which was also used to measure total diaminopimelate before enzymic treatments. The coupled enzymes were also used to prepare pure DD-isomer from chemically synthesized diaminopimelate. A mixture of diaminopimelate isomers was present in walls of four strains of Bacillus megaterium [in each about 75% (w/w) meso-, 18% LL- and 7% DD-] and in walls of two strains of Bacillus cereus (about 85% meso-, 8% LL- and 7% DD-). One strain of B. cereus contained at least 95% meso-diaminopimelate, with only traces of LL- and DD-isomers. Peptidoglycan from Escherichia coli was assayed as containing at least 95% meso-isomer. The proportion of isomers in the wall of a strain of B. megaterium remained constant after growth in a variety of different media.

Amino Acid Isomerases↗