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Biomedical subjects

G Richardson

Publications and source records attributed to G Richardson.

At least 19 recordsLinked to original sources

Distribution of the 275 kD hair cell antigen and cell surface specialisations on auditory and vestibular hair bundles in the chicken inner ear.

The 275 kD hair cell antigen (HCA) is a protein that is specifically associated with the apical surface of sensory hair cells in the chick inner ear. A comparative study of the vestibular and auditory organs of the inner ear, using both wholemounts and cryosections double labelled for the HCA and F-actin, reveals that two distinct types of hair cells can be distinguished on the basis of antibody staining in each of the vestibular epithelia. One type of hair cell has the HCA restricted to the base of the stereocilia bundle and is found in the striolae of the maculae and in a large, centrally located region of each ampulla. The other type of hair cell is found in the extrastriolar regions of the maculae and the peripheral regions of the ampullae and has the HCA distributed over the entire surface of the stereocilia bundle. In the basilar papilla, the auditory epithelium of the chick inner ear, the HCA is, as in the striolar regions of the maculae, restricted to the base of the hair bundles. In all sensory epithelia the HCA is also present on the apical, nonstereociliary surface of the hair cells. Ultrastructural examination of the basilar papilla and the striolar and the extrastriolar regions of the lagenar macula after staining with ruthenium red and tannic acid shows that there are four morphologically different types of interstereociliary connectors (oblique tip connectors, horizontal tip connectors, shaft connectors and basal connectors) associated with the hair bundles. Oblique tip connectors and basal connectors are found on hair cells from all regions and have a similar distribution. Horizontal tip connectors are seen only on hair cells in the basilar papilla and the striolar region of the lagenar macula. Shaft connectors extend all the way to the tips of extrastriolar hair cell bundles, but extend only a short way up the bundles of hair cells in the basilar papilla and striolar region of the lagenar macula. Immunogold labelling confirms the results obtained with immunofluorescence microscopy and demonstrates that the distribution of the HCA on the surface of adjacent stereocilia correlates closely with that of the shaft connectors; i.e., immunostaining is observed up to the tips of the extrastriolar hair cell bundles, but is restricted to the lower regions of hair cell bundles in the striolar region and basilar papilla.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

The effects of flosequinan on hemodynamics and oxygen delivery in cor pulmonale.

The hemodynamic effects of a new orally active vasodilator, flosequinan, were compared with placebo (single blind) over 24 h in eight patients with pulmonary hypertension secondary to severe chronic obstructive pulmonary disease. Mean pulmonary artery pressure was reduced by 5.1 (3.4, 6.7) mm Hg (mean 95 percent CI) (p < 0.003) and pulmonary vascular resistance was reduced by 70 (23, 189) dynes.s.cm-5 (p < 0.013) by active drug compared with placebo. Cardiac output increased significantly with flosequinan by 0.47 (0.03, 0.91) L/min (p < 0.04) and systemic oxygen delivery increased by 90 (50, 120) ml/min/m2) (p < 0.05). A significant reduction in systemic vascular resistance was observed, 132 (35,230) dynes.s.cm-5 (p < 0.02) but no significant changes were seen in systemic arterial blood pressure or arterial blood gas tensions. Flosequinan favorably altered pulmonary hemodynamics relative to systemic and resulted in a significant improvement in oxygen delivery. The hemodynamic and blood gas effects of this compound suggest that it is a promising vasodilator for the treatment of pulmonary hypertension.

Adult

Appearance and distribution of the 275 kD hair-cell antigen during development of the avian inner ear.

The 275 kD hair-cell antigen (HCA) is a protein that was originally identified using immunological techniques in the inner ears of early hatchling and adult chickens. The HCA is specifically associated with the apical surface of sensory hair cells; in the vestibular system the antigen is distributed over the entire stereocilia bundle, but in the auditory system it only extends a short distance up the shafts of the stereocilia. The objectives of this study were to ascertain when the HCA is first expressed during inner ear development, to compare the temporal and spatial patterns of HCA expression with those of neurite ingrowth, and to determine how the distribution of the antigen observed in the auditory system arises during development. Serial sections of otocysts from embryonic day (ED) 4 to ED7.5 (stages 24 to 32) were stained with a monoclonal antibody to the HCA and polyclonal antibodies to the neuron-glial cell adhesion molecule in order to analyse patterns of HCA expression and neurite ingrowth. Nerve fibres are first observed in the anterior pole of the otocyst at ED4.5 (stage 24), and in the evaginating basilar papilla by ED5 (stage 26). The HCA first appears within the vestibular system in the anterior pole of the otocyst at ED5 (stage 26), and within the auditory system in the distal end of the basilar papilla at ED6.5 (stage 29). Serial section analysis indicates that expression of the HCA is always limited to areas of the epithelium where nerve fibres are found, although the delay between the onset of innervation and the onset of HCA expression varies from one region of the otocyst to another. The growth of stereocilia bundles in the auditory system was studied from ED10 to 2 days after hatching in sections from the medial to distal regions of the basilar papilla double labelled with rhodamine phalloidin and monoclonal anti-HCA. At ED12 the stereocilia bundles are 1.7 microns high and the staining observed with both phalloidin and the antibody extend to the same maximum height above the apical surface of the hair cell. The maximum height that anti-HCA staining extends up the stereocilia bundle remains almost constant between ED12 and postnatal day 2, but between ED15 and ED18 the stereocilia bundle grows rapidly in height, with a membrane domain lacking the HCA forming at the distal ends of the stereocilia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

The effects of prenatal alcohol use on the growth of children at three years of age.

In this prospective study of substance use during pregnancy, women were interviewed in their 4th and 7th prenatal months, and women and children were assessed at 24 hr, 8, 18, and 36 months postpartum. Data are presented on the outcome of 519 children at age 3. At 3 years, children who were exposed prenatally to alcohol were smaller in weight, length, and head circumference. They also had an increased number of minor physical anomalies. These effects were found even after controlling for nutritional and environmental factors. The persistence of growth effects at age 3 suggests that children exposed to alcohol prenatally may have a diminished capacity for growth.

Body Height

Prenatal alcohol exposure and offspring growth at 18 months of age: the predictive validity of two measures of drinking.

This is an analysis of the effect of prenatal alcohol exposure on growth of the offspring at 18 months of age. In this prospective study, a cohort of women was interviewed at the end of each trimester of pregnancy, at delivery, and at 8 and 18 months. Offspring were examined at each follow-up point. Two drinking scales, average daily volume (ADV) and frequent heavy drinking (FHD), were used to explore the effect of different patterns of drinking. We found significant relationships between both prenatal FHD and ADV and offspring growth at 18 months. A significant and inverse relationship was found between ADV during the second and the third trimesters of pregnancy and weight, height, and head circumference at 18 months. Frequent heavy drinking during all three trimesters predicted a significant decrease in head circumference at 18 months. FHD during the second trimester was significantly related to weight and height at 18 months. Analyses demonstrated that ADV was a better predictor of growth deficits than FHD.

Adult

Malignant transformation occurring in mature cystic teratomas of the ovary.

Two cases in which tumours of contrasting malignant potential arose in mature cystic teratomas (dermoid cysts) of the ovary are presented: one patient had a spindle-cell sarcoma and the other a trabecular carcinoid. The first patient's clinical course was characterized by rapid recurrence of the tumour and death 3 months after surgery. The second patient is alive and well with no evidence of residual carcinoid, although the follow-up time is short. Since the surgical procedure of choice differs substantially if malignant transformation occurs in an ovarian dermoid cyst, the pathologist should be consulted intraoperatively in selected cases.

Adult

Effect of prenatal alcohol exposure on growth and morphology of offspring at 8 months of age.

In this prospective study of alcohol and other substance use during pregnancy, a cohort of women was interviewed at each trimester of pregnancy and when the offspring were 8 months of age. Data are presented concerning the outcome for 461 infants. A significant relationship was found between alcohol use during pregnancy and the growth and morphology of the offspring at the 8-month follow-up observation. Alcohol use during the second and third trimesters of pregnancy and continuous use of alcohol throughout pregnancy were significantly related to lower weight, length, and head circumference in the exposed infants at the follow-up observation. A significant increase in the risk of minor physical anomalies and fetal alcohol effects was also predicted by prenatal alcohol exposure.

Adolescent

Detectability of emergency lights for underwater escape.

The time to detect each of three underwater lights by six subjects was measured in clear and turbid (attenuation coefficient = 4.2.m-1) water, at distances of 1.54 m and 3.1 m, from two viewing angles, straight ahead (0 degrees) or 65 degrees to one side, and under three levels of ambient illumination. The lights were viewed either through a window, to simulate the use of a face mask, or with the subjects immersed. All lights were detected rapidly (less than 1 s) when viewed through the window in clear water. In turbid conditions, none of the lights was seen at 3.1 m by any subject. At a 1.54 m viewing distance, reliable detection by immersed subjects was found only in the clear water under the two darker ambient illuminations. In turbid water, detection was unreliable. We conclude that the design of underwater escape lighting should not rely on visibility over distances greater than 1.5 m, and that an illuminated guide-bar might provide valuable assistance in directing escape from aircraft.

Accidents, Aviation

Prenatal exposure to alcohol: effect on infant growth and morphologic characteristics.

In this prospective study of alcohol and other substance use during pregnancy, a cohort of 650 women was interviewed at each trimester of pregnancy. Data are presented concerning the status of 595 live singleton births. A relationship was demonstrated between prenatal maternal alcohol use and growth and morphologic abnormalities in the offspring. Low birth weight, decreased head circumference and length, and an increased rate of fetal alcohol effects were all found to be significantly correlated with exposure to alcohol during the first 2 months of the first trimester.

Abnormalities, Drug-Induced

Plasma from myasthenia gravis patients reduces acetylcholine receptor agonist-induced Na+ flux into TE671 cell line.

Plasma from myasthenia gravis patients was tested for its ability to inhibit agonist-induced 22Na+ influx into the TE671 cell line that expresses human acetylcholine receptors. Reduced 22Na+ influx correlated weakly with the total anti-acetylcholine receptor antibody level in the plasma, and was also related to the presence of antibody directed against the agonist binding site, as detected by inhibition of 125I-alpha-bungarotoxin binding. However, in some cases there was inhibition of 22Na+ flux without evident anti-alpha-bungarotoxin binding site antibody. We conclude that in most patients antibodies that interfere with 22Na+ influx do so by blocking the agonist binding site. However, in some cases antibodies may be directed at the Na+ ion channel or some important functional determinant.

Adult

Characterization of immune response to oral administration of Streptococcus sobrinus ribosomal preparations in liposomes.

Gnotobiotic rats gastrically intubated with a total of 12.5 micrograms of Streptococcus sobrinus ribosomal protein incorporated into cholesterol-based liposomes had significantly (P less than or equal to 0.01) fewer carious lesions on their molar surfaces than did nonimmunized infected controls after challenge with a virulent organism. The immunized animals had significantly (P less than or equal to 0.01) lower numbers of molar-adherent S. sobrinus cells and higher levels of salivary immunoglobulin A antibodies to S. sobrinus whole cells and ribosomes than did the control group. Dose-response studies indicated that 12.5 micrograms of S. sobrinus ribosomal protein in liposomes induced slightly higher immune responses than did 62.5, 125.0, and 250.0 micrograms of ribosomal protein incorporated into liposomes. Intubation of rats with up to 250.0 micrograms of S. sobrinus ribosomal protein alone was no more effective in reducing the numbers of molar-adherent S. sobrinus cells than were nonimmunized infected controls, establishing that insertion of ribosomes into liposomes was required for inducing an effective immune response. These results indicate that oral administration of as little as 12.5 micrograms of S. sobrinus ribosomal protein incorporated into liposomes can protect rats from caries formation after challenge with the virulent organism by inducing specific salivary immunoglobulin A antibodies which can inhibit colonization by the challenged S. sobrinus.

Administration, Oral

The suitability of a membrane diffusion growth chamber for studying bacterial interaction.

Rates of diffusion of nutrients and metabolites through 0.1 micron pore diameter polycarbonate membranes are so low that the use of membrane-separated systems to study bacterial interaction seems to have little application. Effective nutrient availability throughout the system is very dependent on membrane area/medium volume ratio. An attempt to demonstrate a known interaction in the membrane diffusion chamber was not successful.

Bacteria

Increased monocyte-mediated cytostasis of lymphoid cell lines in breast and lung cancer patients.

Peripheral blood mononuclear cells of most normal adults and patients with breast or lung cancer were found to inhibit [3H] thymidine uptake by lymphoid cell lines in a growth inhibition assay. At effector:target cell ratios between 5:1 and 20:1, lung cancer patients and breast cancer patients, when compared to normal individuals, demonstrated significantly greater inhibition of [3H] thymidine uptake by a human lymphoid cell line (F-265). The effector cells were adherent and were probably monocytes. Sephadex G-10 column passage or adherence to plastic removed most growth-inhibitory activity. Adherent cells recovered from plastic flasks (88-94% monocytes) were strongly growth-inhibitory. Lung cancer patients receiving BCG immunotherapy were found to have an apparently increased activity compared to patients not treated with BCG. The possible mediation of the growth inhibition by release of prostaglandins was suggested by the reduced cytostatic effects in the presence of indomethacin. Growth-inhibitory activity was not species-restricted, since human effector cells and also effector cells from tumor-bearing mice were reactive against the human target cell and against a murine lymphoma line (RBL-5). Natural killer (NK) cells did not appear to contribute appreciably to the observed cytostasis, since the levels of their activities did not correlate, and human NK cells are non-adherent and have little reactivity against F-265 or RBL-5. The inhibition of [3H]thymidine uptake by target cells was demonstrated to be a good reflection of actual inhibition of proliferation, since incubation of adherent cells from cancer patients with F-265 resulted in similar degrees of reduction in the number of target cells and in [3H] thymidine uptake.

Animals

REM sleep episodes during the Multple Sleep Latency Test in narcoleptic patients.

Forty narcoleptic patients were given the Multiple Sleep Latency Test, consisting of 20 min opportunities to sleep offered at 10.00, 12.00, 14.00, 16.00 and 18.00 o'clock. Eleven patients had 2 episodes of REM sleep, 5 had 3, 11 had 4, and 13 had 5 before they were awakened. Fourteen control subjects given similar opportunities to sleep (reported in a companion article (Richardson et al. 1978)) had no REM sleep episodes. For the 10.00-18.00 o'clock opportunities respectively, there were 32, 29, 30, 28 and 27 REM sleep episodes. We conclude that this procedure can provide physicians with data useful in the diagnosis of narcolepsy.

Adult