We measured intraocular pressures and retinal vascular diameters from 11 subjects during 20 seconds of microgravity produced by parabolic flight on board a KC-135 aircraft. Intraocular pressures increased 58% during parabolic flight compared to baseline values (19 +/- 1 mm Hg vs 12 +/- 1 mm Hg, respectively; P < .001). A 4% reduction in the caliber of retinal arteries was also noted during microgravity, but this change did not achieve statistical significance (7.8 +/- 0.3 pixels at zerogravity vs 8.1 +/- 0.3 pixels at 1g; P = .07). The increase in intraocular pressure and trend of arteries to constrict are thought to result from cephalad shifts in intravascular and extravascular body fluids as a result of the absence of the 1g hydrostatic gradient. The results of our study confirm that this fluid shift and its effects on the eye occur rapidly, within 20 seconds of exposure to microgravity.

Adult↗

PubMed1993

Crystallization and preliminary X-ray studies of influenza A virus neuraminidase of subtypes N5, N6, N8 and N9.

Neuraminidase heads from the following subtypes of influenza A virus have been crystallized: N5, N6, N8 and whale virus N9. The last three yielded crystals of X-ray diffraction quality; the N5 crystals obtained so far are not suitable for high resolution studies. The cell dimensions and space groups of crystals grown from the four subtypes have been determined.

Crystallography↗

PubMed1993

Electrophysiological properties and chemosensitivity of acutely isolated nodose ganglion neurons of the rabbit.

Neurons in the nodose ganglion were enzymatically dissociated from adult rabbits and electrophysiologically examined within 2 h. About 90% of the neurons survived the dissociation procedure. Their resting membrane potential (-59 +/- 0.6 mV), time constant (5.7 +/- 0.5 ms), input resistance (80 +/- 5.3 M omega), action potential properties (amplitude, 79 +/- 1.2 mV; overshoot 21 +/- 1.0 mV; duration 5.2 +/- 0.1 ms; threshold, -38 +/- 0.9 mV; and fast spike afterhyperpolarization, 10 +/- 0.5 mV, 64 +/- 3.8 ms) were not different from values obtained from nodose neurons in intact ganglion in vitro and in vivo. An unusually long duration spike afterhyperpolarization observed in about 35% of nodose neurons in intact ganglion was demonstrated in about 28% of the acutely isolated neurons. The percentage of isolated neurons responding to bath applied acetylcholine, bradykinin, serotonin and histamine was similar to those reported for neurons in the intact ganglia. We conclude that the electrophysiological and chemoreceptive properties of acutely isolated adult rabbit nodose neurons are similar to those observed for neurons in intact ganglia. Thus the availability of large numbers of acutely isolated adult nodose neurons should allow multidisciplinary studies of vagal afferent C-fiber neurons not readily obtainable in the intact ganglion.

Action Potentials↗

PubMed1993

Bullous pemphigoid and autoimmunity.

BACKGROUND: There are many case reports of bullous pemphigoid (BP) in association with a variety of autoimmune disorders, but no large case controlled studies have been performed. OBJECTIVE: Our purpose was to determine whether there is an increased incidence of autoimmune disorders in patients with BP and whether there is a particular haplotype associated with this. METHODS: A total of 108 patients with BP were studied and compared with a group of 108 age- and sex-matched controls. HLA typing at the A, B, C, and DR loci was performed on 55 of the 108 patients with BP. RESULTS: The difference in incidence of autoimmune disorders between patients and controls was not significant. The haplotypes of patients with BP were similar to those of a locally drawn population. CONCLUSION: There is no increase in the incidence of autoimmune disorders in BP, and no particular haplotype appears to be associated with a predisposition to this condition.

Aged↗

PubMed1993

Bullous pemphigoid and associated autoimmune thrombocytopenia: two case reports.

We describe two patients with bullous pemphigoid in whom autoimmune thrombocytopenia developed. Only one case of bullous pemphigoid associated with autoimmune thrombocytopenia has previously been reported, and in that case, autoimmune hemolytic anemia was also present (Evans' syndrome). However, a wide range of other autoimmune diseases have been described in association with bullous pemphigoid, and this literature is reviewed.

Autoimmune Diseases↗

PubMed1993

Conformational constraints of conserved neutralizing epitopes from a major antigenic area of human respiratory syncytial virus fusion glycoprotein.

To study the conformational requirements of epitopes from a conserved antigenic area (area II) of respiratory syncytial (RS) virus fusion (F) glycoprotein, peptides of increasing length containing amino acids essential for these epitopes were synthesized. The synthetic peptides were tested for binding to a panel of neutralizing monoclonal antibodies (MAbs) for this area as well as to rabbit hyperimmune and human convalescent antisera. Antibody binding was dependent on peptide length; thus, a 61-residue peptide spanning amino acids 215 to 275 of the F1 subunit (peptide F215-275) reacted with more antibodies than a shorter (41-residue) peptide F235-275, and this one with more than the (21-residue) peptide F255-275. Most human convalescent sera contained antibodies that reacted with peptides F215-275 and F235-275 but failed to react with F255-275. The results of antibody binding could be related to the structure adopted by the peptides in solution, as determined by circular dichroism spectroscopy and susceptibility of peptides to trypsin digestion. Pretreatment of peptide F215-275 with SDS abolished reactivity with certain MAbs, supporting the notion that higher order structures were needed for antibody binding. High titre anti-peptide antisera were induced in rabbits inoculated with the peptides; however, these sera failed to react with the native F molecule. In mice, only the largest F215-275 peptide induced an anti-peptide response, but their sera reacted poorly with the native F protein and the animals were not protected against an RS virus challenge. These results illustrate the potential use of synthetic peptides in studies of the F protein physical and antigenic structures as well as the problems in designing synthetic RS virus vaccines.

Amino Acid Sequence↗

PubMed1993

Suction-induced basal cell cytolysis in the Weber-Cockayne variant of epidermolysis bullosa simplex.

In the Weber-Cockayne form of epidermolysis bullosa simplex (EBS-WC), trauma induces blisters which are confined to the palms and soles. Histologically, basal cell cytolysis is seen. We studied 6 patients with EBS-WC to determine the ultrastructural level at which artificially-induced suction blisters form. Blisters were raised by application of a suction blister cup to uninvolved forearm skin, the cup being connected to a negative pressure of 200 mm of mercury. The blisters were biopsied and examined by light and electron microscopy. On light microscopy, all biopsies showed marked vacuolization of keratinocytes in the lower two-thirds of the epidermis, and in all but one there was a cleavage plane through the basal keratinocytes. These findings were confirmed by electron microscopy in 4 patients. The separation through the basal cells is in contrast to the situation in normal individuals in whom cleavage occurs below the level of the basal cells, within the lamina lucida. Thus, even apparently normal skin from non-acral sites has the same structural abnormality as the affected acral sites in EBS-WC.

Adolescent↗

PubMed1993

Mechanisms of action of Pseudomonas aeruginosa pyocyanin on human ciliary beat in vitro.

Pyocyanin is a blue redox active pigment produced by Pseudomonas aeruginosa. It is present at concentrations of up to 10(-4) M in sputa from patients with cystic fibrosis and bronchiectasis who are heavily colonized with this organism. Pyocyanin, at physiologically relevant concentrations, slows human nasal ciliary beat frequency (CBF) in vitro and leads to disruption of the epithelium. Pyocyanin-induced slowing of CBF after 2 h was associated with a significant fall in intracellular cyclic AMP (cAMP) (90%) and ATP (66%) and was reversible after the pyocyanin was removed by washing. These effects were not mediated through interaction with neutrophils. The pyocyanin-induced fall in CBF was not affected by EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid], pyrazinamide, 8-phenyltheophylline, indomethacin, or antioxidants, including catalase (500 U/ml), superoxide dismutase, and N-acetylcysteine. Ciliary slowing was, however, prevented (> 70%) by isobutylmethylxanthine and forskolin, both of which increase intracellular cAMP, and also by the cAMP analog, dibutyryl cAMP. There was also a concomitant protection against the fall in both cAMP and ATP. These agents also delayed the onset of epithelial disruption associated with pyocyanin treatment. In contrast, treatment with the iron chelator desferrioxamine prevented epithelial disruption, although it had no effect on pyocyanin-induced slowing of CBF. It appears that ciliary slowing can be dissociated from epithelial disruption and that the effects of pyocyanin on CBF are associated with a fall in both intracellular cAMP and ATP.

Adenosine Triphosphate↗

PubMed1993

Effect of hyperventilation and mental stress on coronary blood flow in syndrome X.

OBJECTIVES: To assess the effect of hyperventilation and mental stress on coronary blood flow and symptom production in patients with syndrome X. DESIGN: A prospective study. Hyperventilation and mental stress tests were performed on the ward and were repeated in the cardiac catheter laboratory where coronary blood flow velocity was also measured with an intracoronary Doppler catheter in the left anterior descending coronary artery. Oesophageal manometry studies were also performed. PATIENTS: 29 patients with syndrome X (typical anginal chest pain, a positive exercise test, and normal coronary angiogram). SETTING: A regional cardiothoracic centre. RESULTS: Hyperventilation produced typical chest pain in 16 patients on the ward. 13 patients experienced their typical chest pain with mental stress test 5. Ten patients experienced chest pain with both hyperventilation and mental stress tests. This pattern was reproduced exactly when the tests were repeated in the cardiac catheter laboratory. Hyperventilation produced a significant increase in the rate-pressure product during ward and laboratory testing. There was, however, no significant change in the rate-pressure product on mental stress tests. The mean (SEM) coronary flow velocity decreased significantly on hyperventilation in the catheter laboratory from 10.0 (0.92) cm/s to 5.9 (0.72) cm/s (p < 0.001). There was also a significant reduction in the mean (SEM) coronary blood flow velocity on mental stress tests from 9.8 (0.86) cm/s to 7.4 (0.6) cm/s (p < 0.001). This reduction in flow velocity occurred in the absence of any changes in diameter of the left anterior descending artery. Further analysis showed that the coronary flow velocity was reduced significantly in only that group of patients in which hyperventilation and mental stress provoked chest pain. There was a significant increase in the arterial concentrations of noradrenaline on both hyperventilation and mental stress testing. Oesophageal manometry showed abnormalities in 17% of patients. CONCLUSIONS: Both hyperventilation and mental stress can produce chest pain in patients with syndrome X and this is associated with a reduction in coronary blood flow velocity. The results of this study suggests that this reduction in coronary flow occurs as a result of increased microvascular resistance.

Adult↗

PubMed1993

Coronary flow reserve measurements with a new Judkins-style Doppler angiographic catheter.

The authors assessed whether measurements obtained by Judkins-style Doppler catheters are comparable to those achieved with the intracoronary Doppler technique in 42 patients with normal coronary arteries on angiography (19 syndrome X and 23 heart transplant patients). Resting coronary flow velocity and response to a hyperemic intracoronary dose of papaverine was measured with a Judkins-style, 8F Doppler-tipped catheter positioned in the left coronary ostium and a 3.6F intracoronary Doppler catheter positioned in the proximal left anterior descending artery. Mean coronary flow velocity at rest was significantly higher with the Judkins Doppler (10.1 +/- 4.6 vs 6.3 +/- 4.5 cm/sec, p < 0.01). The mean coronary flow velocity at peak hyperemia was also significantly higher with the Judkins Doppler (33.7 +/- 14.1 vs 19.7 +/- 11.5 cm/sec, p < 0.01). Coronary flow reserve was 3.57 +/- 1.3 with the Judkins Doppler and 3.47 +/- 1.2 with the intracoronary Doppler (r = 0.85). A second study was performed in 14 heart transplant patients with the intracoronary Doppler positioned in the left main coronary artery. The resting and hyperemic flow velocities were again higher with the Judkins Doppler but the differences were not statistically significant. There was again a strong correlation between the Doppler catheters for coronary flow reserve measurements. The Judkins-style Doppler technique appears to be a quick, safe, and accurate alternative to the intracoronary Doppler technique.

Cardiac Catheterization↗

PubMed1993

The outcome of school dental screening in two suburban districts of Greater Manchester, UK.

School dental screenings have been carried out in the community dental service for over eighty years but there have been very few evaluations of their outcome. The community dental service is now required to provide treatment only for those who have experienced difficulty in obtaining treatment in the general dental service. A follow up procedure to school dental screenings was designed to ensure that as many children in need of treatment as possible attended a general dental practitioner. The objective of this study was to evaluate the effectiveness of this procedure in persuading school children to attend a general dental practitioner. Data on the outcome of this follow up procedure were collected between May 1990 and March 1991 in Oldham and Tameside and Glossop. Of the 47,776 pupils screened, 10,925 were considered to require treatment. General dental practitioners confirmed subsequent attendance by 2,083 (19 per cent) and attendance at community dental service clinics was confirmed for a further 363 (3 per cent). A further 2,161 (20 per cent) were found to have received treatment at a rescreening held two to three months later. Of those referred for treatment, 4,607 children (42 per cent) had received it within the three months following the screening, the majority having received care in the general dental service.

Child↗

PubMed1992

Nitric oxide synthase in macula densa regulates glomerular capillary pressure.

Tubular-fluid reabsorption by specialized cells of the nephron at the junction of the ascending limb of the loop of Henle and the distal convoluted tubule, termed the macula densa, releases compounds causing vasoconstriction of the adjacent afferent arteriole. Activation of this tubuloglomerular feedback response reduces glomerular capillary pressure of the nephron and, hence, the glomerular filtration rate. The tubuloglomerular feedback response functions in a negative-feedback mode to relate glomerular capillary pressure to tubular-fluid delivery and reabsorption. This system has been implicated in renal autoregulation, renin release, and longterm body fluid and blood-pressure homeostasis. Here we report that arginine-derived nitric oxide, generated in the macula densa, is an additional intercellular signaling molecule that is released during tubular-fluid reabsorption and counters the vasoconstriction of the afferent arteriole. Antibody to rat cerebellar constitutive nitric oxide synthase stained rat macula densa cells specifically. Microperfusion of the macula densa segment of single nephrons with N omega-methyl-L-arginine (an inhibitor of nitric oxide synthase) or with pyocyanin (a lipid-soluble inhibitor of endothelium-derived relaxation factor) showed that generation of nitric oxide can vasodilate the afferent arteriole and increase glomerular capillary pressure; this effect was blocked by drugs that prevent tubular-fluid reabsorption. We conclude that nitric oxide synthase in macula densa cells is activated by tubular-fluid reabsorption and mediates a vasodilating component to the tubuloglomerular feedback response. These findings imply a role for arginine-derived nitric oxide in body fluid-volume and blood-pressure homeostasis, in addition to its established roles in modulation of vascular tone by the endothelium and in neurotransmission.

Amino Acid Oxidoreductases↗

PubMed1992

Antithrombotic effect of beta,beta'-monochloromethylene diadenosine 5',5"'-P1,P4-tetraphosphate.

The feasibility of using beta,beta'-monochloromethylene diadenosine 5',5"'-P1,P4-tetraphosphate (AppCHCl-ppA) as an antithrombotic agent was studied in a rabbit intracarotid cannula thrombosis model previously shown to be sensitive to antiplatelet agents. This analogue, having a P-C-P bridge in place of a P-O-P internucleoside linkage, has been found resistant to phosphodiesterase activity. Rabbits were infused with the dinucleotide at a dose of 50 mg per kg over a 2-hr period, at a controlled rate by pump. A 1-cm length of polyethylene cannula (1 mm i.d.) was tied into the carotid artery. Animals were stable under general anesthesia during the entire period of the experiment. In the control group, 16 of 20 animals formed clots, an incidence of 80%, whereas in the test animals, 6 of the 20 formed clots (30% incidence, P < 0.05). After preincubation of whole blood with 50 microM AppCHClppA at 37 degrees C for up to 3 hr, a consistent suppression of ADP-induced platelet aggregation was observed. The present study suggests that AppCHClppA may be useful as an antithrombotic agent in certain clinical situations, such as hemodialysis, arteriovenous shunts, and introduction of artificial heart valves. It may also possibly prevent extension of recent clots. The toxicity and metabolism of AppCHClppA have, however, yet to be explored.

Animals↗

PubMed1992

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