Gastro-oesophageal reflux and the lung.
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Cystic Fibrosis↗
Biomedical subjects
H Smith
Publications and source records attributed to H Smith.
Does the vestibulo-ocular reflex (VOR) merit redefinition?
The VOR has historically been described by parameters of the slow phase of nystagmus while fast phases have been systematically ignored. However, ample neurophysiologic and theoretical evidence suggests that fast phases are an integral part of the VOR and are not to be discarded in evaluation of vestibular function. In a series of experiments, normal subjects and compensated patients with total or partial loss of unilateral peripheral vestibular function were tested. They were exposed to sinusoidal oscillations (20 degrees, 60 degrees, and 120 degrees/second at 1/6 Hz and 25 degrees/second at 1 Hz) with no actual or imaginary visual targets (doing mental arithmetic) and the usual slow-phase parameters (gain, phase, etc.) were computed. The gaze (total eye position, slow and fast phase of nystagmus vs. head + head position in space) was also plotted vs. head position in space. It was found that in patients, fast phases of nystagmus are unequally (right vs. left) produced, extending the linear range of VOR function. It was also found that in normal subjects and patients, gaze essentially tracks the head in the absence of visual targets. It is concluded that fast phases of nystagmus contribute to gaze control during head rotations in darkness and that the definition and the testing of the VOR have to be modified to accommodate these observations.
Eye Movements↗
Viral-like characteristics of particle aggregates in a lymphoblastic cell line.
A lymphoblastic cell line (K45) established from a child with acute lymphoblastic leukemia (ALL) is characterized by a profusion of intracytoplasmic particle aggregates (PA) similar in morphology to those occurring in fresh childhood ALL cells. The PA in K45 cells were examined for morphology and capacity for nucleic acid synthesis to test the hypothesis that they are identical to those in fresh ALL cells, and also to identify characteristics which might distinguish PA from cell organelles and which might determine if they are viral-like. In contrast to cell organelles, the PA in both K45 and ALL cells were found to be characterized by a localized thickening of the particle wall. Furthermore, autoradiography of K45 cells showed uptake by PA of 3H uridine rather than 3H thymidine indicating an RNA composition. The presence of PA in profusion was associated with, but preceded necrotic death of K45 cells. These combined features suggest that the PA in K45 and in ALL cells are identical, that they are distinct from cell organelles, are not formed as a consequence of the initiation of cell death and that, while their exact nature remains unknown, a viral origin cannot be excluded.
Autoradiography↗
Families, parks, gardens and toxocariasis.
Toxocara canis antibody titres were measured in members of 30 families. 73/140 (52.1%) family members were seropositive for T. canis at a dilution greater than or equal to 1:50 and 11 (7.8%) had reciprocal titres greater than or equal to 800. Toxocara ova were sought (a) in relation to the 30 families and (b) in the community. No toxocara ova were found in household dust samples. 38% of family gardens contained toxocara ova while 6% of soil samples from public parks and open spaces around housing estates were positive. None of the faecal specimens from pet dogs were positive for toxocara ova as compared to 6.2% of stray dogs. 5.3% of canine faecal samples from the streets contained toxocara ova. In this study household garden soil was a potentially greater source of toxocara infection than soil in public parks and open spaces.
Adolescent↗
Rhenium-186(Sn)HEDP for treatment of painful osseous metastases: results of a double-blind crossover comparison with placebo.
Rhenium-186 (tin) hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that simultaneously localizes in multiple skeletal metastases in patients with advanced cancer. A single intravenous administration of 30-35 mCi (1110-1295 MBq) is associated with a prompt, significant relief of osseous pain in about 80% of such patients. The efficacy of this new compound was evaluated further by utilizing a double-blind crossover comparison with 99mTc-methylene diphosphonate (MDP) as a radioactive placebo. The new rhenium compound resulted in a significantly (p less than 0.05) greater decrease in pain than did treatment with the radioactive placebo. Rhenium-186(Sn)HEDP appears to be a useful new compound for the palliation of painful skeletal metastases.
Aged↗
Nitrendipine once or twice daily in hypertensive non-insulin-dependent diabetes mellitus.
Twenty (12 male, 8 female) hypertensive patients were recruited into the study; their mean (+/- SD) sitting blood pressure (BP) was 166 +/- 13/101 +/- 4 mm Hg, age 59.6 +/- 5.8 years, weight 83.4 +/- 14.2 kg, and glycosylated hemoglobin (HbA1) 9.9 +/- 2.6%. After a run-in period of 4 weeks, patients were randomized to receive nitrendipine once or twice daily, with 15 patients completing the 12-week study period. Prior to treatment with nitrendipine, the patients subsequently treated on a twice-daily regimen had a higher sitting systolic BP (SBP) of 173 +/- 15 mm Hg compared to the once-daily patient group at 159 +/- 7 mm Hg (p less than 0.05). There were no differences between the two treatment groups in weight or diabetes control. Once-daily nitrendipine effectively reduced the sitting SBP and diastolic BP (DBP), i.e., SBP fell from 159 +/- 7 to 147 +/- 12 mm Hg (p less than 0.05) and DBP fell from 100 +/- 4 to 86.3 +/- 8 mm Hg (p less than 0.001). Nonsignificant reductions in weight from 81.5 +/- 11.3 to 80.9 +/- 11.2 kg and HbA1 from 9.8 +/- 3.3 to 8.4 +/- 1.3% were also seen. Similarly, with twice-daily nitrendipine, a significant (p less than 0.01) fall in sitting systolic BP from 173 +/- 15 to 148 +/- 9 mm Hg and DBP 103 +/- 4 to 85 +/- 8 mm Hg was also achieved. Little or no change was observed in weight or glycemic control in this patient group.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Intravenous insulin simulates early insulin peak and reduces post-prandial hyperglycaemia/hyperinsulinaemia in type 2 (non-insulin-dependent) diabetes mellitus.
In NIDDM patients the deficient initial rise in insulin is a consistent finding. This early phase of insulin secretion influences the degree of hyperglycaemia following a meal. In this study insulin was infused intravenously into newly diagnosed NIDDM patients in an attempt to mimic the non-diabetic insulin response to a mixed meal and to determine the effect of early insulin availability on post-prandial glucose, C-peptide and insulin concentrations in NIDDM patients. The study involved standardized meal tolerance tests (MTT) with and without insulin on 2 separate days, 1 week apart. Insulin was given by intravenous infusion (2.5 U Actrapid over 30 min) immediately following the start of a 500 kcal MTT. The subjects were divided into non-obese and obese sub-groups with 8 subjects in each group (BMI 24.0 vs 32.0 kg/m2, HbA1, 12.7 vs 9.8%, age 44.4 vs 43.0 yrs, respectively). Following intravenous insulin in non-obese diabetics a peak plasma insulin concentration of 0.393 pmol/ml was observed at 15 min compared to 0.148 pmol/ml at 90 min without exogenous insulin. The post-prandial glucose excursion between 60 and 120 min was significantly lowered with insulin (p less than 0.01). Similarly in the obese patients a higher and earlier insulin peak was achieved with intravenous insulin, with a lower level during the second half of the 4 h post-prandial period, the difference reaching significance at 150 min (p less than 0.05). No differences were observed in the C-peptide concentrations between the 2 study days.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Resistance to human serum of gonococci in urethral exudates is reduced by neuraminidase.
Gonococci examined directly from urethral exudates are resistant to killing by human serum, but most strains become susceptible on subculture. Previous work with gonococci grown in vitro indicates that resistance in vivo is due to sialylation of gonococcal lipopolysaccharide (LPS) by a host factor, cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NANA) or a related compound present in urogenital secretions and blood cells including phagocytes, which exude during inflammation. This sialylation inhibits the reaction between bactericidal IgM in serum and its target LPS sites. Here, we confirm the indication by using gonococci grown in vivo. Crucial to the above conclusions was the marked reduction of CMP-NANA-conferred serum resistance when gonococci were treated with neuraminidase to remove sialyl groups from their LPS. We now show that the serum resistance of gonococci in urethral exudates was reduced by treatment with neuraminidase from more than 95% (calculated in relation to controls incubated with heated serum) to 2-11% according to sample and incubation time. Subculture of the gonococci also reduced resistance to 9-11% but resistance was restored to more than 95% by incubation with CMP-NANA. This work is the culmination of an investigation that underlines the need to identify specific host factors and the virulence determinants they induce in vivo in future studies of pathogenicity.
Blood Bactericidal Activity↗
In vitro and in vivo modification of Neisseria gonorrhoeae lipooligosaccharide epitope structure by sialylation.
After growth of gonococci in the presence of cytidine monophospho-N-acetyl-neuraminic acid (CMP-NANA), their 4.5-kD lipooligosaccharide (LOS) component was increased by approximately 400 daltons, whereas the LOS of strains lacking the 4.5-kD component were unaffected. Expression of mAb-defined epitopes on the 4.5-kD component was decreased on LOS of strains grown in CMP-NANA, and treatment of the LOS with neuraminidase reversed this affect. Gonococci incubated with human PMNs also had decreased expression of the 4.5-kD+ epitopes. A detergent extract of gonococci incorporated radiolabeled NANA in the LOS, suggesting the presence of a sialyltransferase in gonococci. Exogenous sialyltransferases also could use LOS as an acceptor.
Animals↗
A surface polysaccharide forms when gonococci are converted to serum resistance by cytidine 5'-monophospho-N-acetyl neuraminic acid.
A serum-susceptible, guinea-pig chamber-passaged, laboratory strain (BS4 (agar)) of Neisseria gonorrhoeae was converted to serum resistance by incubation with cytidine 5-monophospho-N-acetyl neuraminic acid (CMP-NANA) and examined by electron microscopy after staining with ruthenium-red. In contrast to serum susceptible gonococci incubated without CMP-NANA, the majority (60-70%) of the serum resistant organisms showed a surface accumulation of polysaccharide. This surface polysaccharide was enhanced on all the resistant gonococci after incubation with fresh human serum. Control susceptible gonococci were devoid of the polysaccharide after incubation with heated human serum. Identical results were obtained with a fresh gonococcal isolate which had lost serum resistance on subculture but which, in common with 3 other isolates, was restored to serum resistance by incubation with CMP-NANA.
Animals↗
The effect of drugs on lung hyperreactivity in Sephadex treated rats.
The injection of Sephadex G200 intravenously into rats induced a blood eosinophilia and an hyper-reactivity of lung parenchymal strips to 5-hydroxytryptamine (5HT) and carbachol. The blood eosinophilia and the hyper-reactivity to 5HT reached a maximum at the same time and before that to carbachol. It was shown previously that the reduction of the blood eosinophilia by treatment with dexamethasone, dapsone, phenidone, isoprenaline and aminophylline also reduced the hyper-reactivity to 5HT. In this study we found that only dexamethasone reduced the hyper-reactivity to carbachol.
Animals↗
Molecular cloning of the Salmonella typhimurium lep gene in Escherichia coli.
A system is described which enabled the selection of a heterologous lep gene, encoding signal peptidase I, in Escherichia coli. It is based on complementation of an E. coli mutant, in which the synthesis of signal peptidase I can be regulated. With this system the lep gene of Salmonella typhimurium was cloned and the nucleotide sequence was determined. The S. typhimurium lep gene encodes a protein of 324 amino acids. Expression of the gene in the E. coli mutant resulted in suppression of growth inhibition and in the restoration of processing activity under conditions where synthesis of E. coli signal peptidase I was repressed. The cloned S. typhimurium signal peptidase I had an apparent molecular weight of 36,000 daltons, which is in agreement with the calculated molecular weight of 35,782 daltons. The system described for selection of the S. typhimurium lep gene may permit the cloning and expression of other heterologous signal peptidase I genes.
Amino Acid Sequence↗
Effects of isoprenaline, adrenaline and selective alpha 1- and alpha 2- adrenoceptor stimulation on hypoxic pulmonary vasoconstriction in rat isolated perfused lungs.
In the rat pulmonary vasculature perfused with blood in situ vasoconstriction induced by hypoxia was reversed by isoprenaline (doses greater than 1 ng) and adrenaline (doses greater than 30 ng) and exacerbated by phenylephrine but not UK 14304. Doses of adrenaline less than 30 ng had no effect, except in the presence of propranolol (1 microM) or phentolamine (3 microM) when they caused vasoconstriction and vasodilation respectively, showing that, at dose levels less than 30 ng, adrenaline's beta- adrenoceptor vasodilator properties were balanced by its alpha- adrenoceptor vasoconstrictor properties. The pressor effects of adrenaline, in the presence of propranolol, were antagonised by prazosin (0.1 microM) but not by equi-molar concentrations of rauwolscine. These results suggest that the alpha- adrenoceptor agonist property of adrenaline is of benefit to its use as an inhaled bronchodilator because unopposed beta- adrenoceptor stimulation can reverse hypoxic pulmonary vasoconstriction in poorly ventilated regions of the lung, promote further ventilation/perfusion mismatching and lower PaO2. They further suggest that adrenaline affects pulmonary vascular tone in the rat via alpha 1- adrenoceptors, stimulation of alpha 2- adrenoceptors having no effect.
Adrenergic alpha-Agonists↗
Preventive treatment of asymptomatic left ventricular dysfunction following myocardial infarction.
Progressive asymptomatic ventricular dilatation can occur following myocardial infarction and severe ventricular dysfunction is often present by the time clinical congestive heart failure occurs. In a randomized, double-blind trial, the effects of captopril 25 mg tid, frusemide 40 mg daily and placebo were studied in 90 patients with asymptomatic left ventricular dysfunction (ejection fraction less than 45%) 1 week following Q wave myocardial infarction. Left ventricular volumes and function were assessed at intervals during the subsequent year using two-dimensional echocardiography. The frusemide and placebo groups showed significant increases in ventricular volumes with stroke volume index unchanged and ejection fraction slightly reduced, whereas the captopril group showed a significant reduction in left ventricular end-systolic volume index with stroke volume index and ejection fraction increased. At 12 months the difference in the change in ejection fraction from baseline between the captopril and frusemide groups was 10.5% and captopril and placebo groups 9.6% (both P less than 0.0001). There was a significant difference in occurrence of clinical heart failure in the placebo group compared with the other groups (P less than 0.05). Blood pressure increased significantly within the normal range in the placebo and frusemide groups whereas there was essentially no change from baseline in the captopril group. There was no significant correlation between baseline left ventricular volumes and function and subsequent change, and anterior and inferior infarct subgroups showed similar responses within the treatment groups. In conclusion, captopril improves asymptomatic ventricular dysfunction and prevents clinical heart failure during the year following myocardial infarction. Frusemide may also prevent clinical heart failure but not progressive ventricular dilatation.
Adult↗
Lack of a role of the duodenal microflora in pathogenesis of persistent diarrhea and diarrhea-related malabsorption in Peruvian children.
Although few episodes of diarrhea last longer than 14 days these episodes are particularly associated with growth faltering and malnutrition. We have examined the role of the duodenal microflora in prolonging diarrhea in Peruvian children ages 3 to 36 months by comparing the microflora in 89 children with persistent diarrhea, 38 children with acute diarrhea and 34 diarrhea-free controls from the same environment. Bacteria were retrieved from 93% of all aspirates, including 94% of those from controls. There were no significant differences among the 3 groups with respect to total bacterial count, to the proportion of children with duodenal Enterobacteriaceae and to the proportion with anaerobes, lending no support to the hypothesis that proliferation of bacteria in the small intestine during the acute illness prolongs diarrhea. When only children older than 18 months were compared, anaerobes were cultured more frequently from those with persistent diarrhea than from controls, but the presence of anaerobes was not associated with adverse clinical outcome. Although malabsorption, especially steatorrhea, was common, there was no association between elevated bacterial counts and fecal loss of nutrients in 69 children who received the same diet. In this population steatorrhea could not be attributed to bacterial overgrowth.
Acute Disease↗
Pathogenicity and the microbe in vivo. The 1989 Fred Griffith Review Lecture.
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Animals↗
Phytochrome Effects on the Relationship between Chlorophyll and Steady-State Levels of Thylakoid Polypeptides in Light-Grown Tobacco.
The effects of phytochrome status on chlorophyll content and on steady-state levels of thylakoid proteins were investigated in green leaves of Nicotiana tabacum L. plants grown under white light. Far-red light given either as a pulse at the end of each photoperiod, or as a supplement to white light during the photoperiod, reduced chlorophyll content per unit area and per unit dry weight. These differences were also observed after resolving chlorophyll-containing polypeptides by gel electrophoresis. Chlorophyll a:b ratio was unchanged. Both Coomassie blue-stained gels and immunochemical analyses showed that, in contrast to the observations in etiolated barley (K Apel, K Kloppstech [1980] Planta 150: 426-430) and pea (J Bennett [1981] Eur J Biochem 118: 61-70) seedlings, and in etiolated tobacco leaves (this report), in fully deetiolated tobacco plants changes in chlorophyll content were not correlated with obvious changes in the steady-state levels of thylakoid proteins (e.g. light-harvesting, chlorophyll a/b-binding proteins).
Journal Article↗
Acute lymphoblastic leukaemia with cytoplasmic granules or inclusions.
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Child↗