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Biomedical subjects

J Henderson

Publications and source records attributed to J Henderson.

At least 19 recordsLinked to original sources
PubMed1992

Relative resistance to 1,25-dihydroxyvitamin D3 in a keratinocyte model of tumor progression.

We have examined the effect of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on mitogen-stimulated growth and on c-myc proto-oncogene expression in a keratinocyte model of tumor progression. A dose-dependent inhibition of cell growth by 1,25-(OH)2D3 was demonstrated in both established (HPK1A) and malignant (HPK1A-ras) cells. However, this inhibition was observed with the addition of 1,25-(OH)2D3 at a higher concentration in HPK1A-ras cells than in HPK1A cells. Cell cycle analysis revealed a blockage of the normal progression of the cell cycle from G0 to S phase in the presence of 1,25-(OH)2D3. A higher concentration of 1,25-(OH)2D3 was required in HPK1A-ras cells to overcome the mitogen-stimulated progression into S phase, when compared with HPK1A cells. Analysis of c-myc messenger RNA revealed a strong inhibition of its expression at early time points with higher concentrations of 1,25-(OH)2D3 being required to obtain an inhibition in HPK1A-ras cells similar to that obtained in HPK1A cells. 1,25-(OH)2D3 receptor characterization by sucrose gradient analysis and equilibrium binding demonstrated the presence of a single 3.7 S protein with similar receptor numbers and affinity in both cell lines. These observations therefore demonstrate that an alteration of the growth inhibitory response to 1,25-(OH)2D3 occurs when keratinocytes acquire the malignant phenotype and suggest that the alteration lies beyond the interaction of the ligand with its receptor. In addition, relative resistance to 1,25-(OH)2D3 was also observed in the expression of the cell-cycle associated oncogene c-myc. These studies may therefore have important implications in vivo in the development and growth of epithelial cell cancers.

Animals↗
PubMed1992

Localization of inhaled trimellitic anhydride to lung with a respiratory lymph node antibody secreting cell response.

Male Sprague-Dawley rats were exposed to trimellitic anhydride (TMA) by inhalation (500 micrograms/m3), 4 hours a day, for 1 to 10 days. TMA was localized to lung cells by immunoelectron microscopy. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used in an attempt to localize TMA to lung lavage proteins. The lung-associated lymph node (LALN) B-lymphocyte response was measured by quantitation of immunoglobulin (Ig)G, IgA, and IgM antibody secreting cells specific for TMA rat serum albumin (TM-RSA) by use of the enzyme-linked immunospot assay (ELISPOT) method. The IgG, IgM, and IgA antibody response to TM-RSA in serum and lavage fluid was quantitated by ELISA. Lung injury was assessed by the number of external lung hemorrhagic foci and lung weight. Immunoelectron microscopy localized TMA to alveolar and bronchial cells on all exposure days. ELISA detected trace amounts of TMA haptenized lavage proteins that could not be detected by Western blot analysis. A marked increase occurred in lung injury from day 7 to 10. The LALN IgG, IgA, and IgM antibody secreting cell response to TM-RSA paralleled measures of lung injury. IgG, IgM, and IgA serum and lavage antibody to TM-RSA were correlated with lung injury measures. Lavage and serum IgG antibody levels had the highest correlation with lung injury.

Administration, Inhalation↗
PubMed1992

Effect of heparin surface modification of polymethylmethacrylate intraocular lenses on signs of postoperative inflammation after extracapsular cataract extraction. One-year results of a double-masked multicenter study.

PURPOSE: A heparin surface modified posterior chamber intraocular lens (IOL) was compared with a conventional polymethylmethacrylate (PMMA) IOL regarding postoperative complications caused by inflammation. METHODS: Five hundred twenty-four patients from 10 different centers were included in a parallel group, double-masked, multicenter study. RESULTS: The cumulative number of patients with inflammatory cellular deposits on their IOLs during the first postoperative year differed significantly in favor of the heparin surface modified group, with 29.8% of the patients having cellular deposits compared with 48.8% of patients in the control group. Cellular deposits were observed most frequently at 3 months after surgery, and the difference between the groups was most pronounced and statistically significant at this time. The same results were seen at 1 year, but the difference was not significant. The number of cellular deposits per patient, however, was significantly lower in the heparin surface modified group at 1 year. Cumulatively, there were significantly more patients with posterior synechiae in the PMMA group than in the heparin surface modified group during the 1-year follow-up. Complications were few and comparable between the groups. CONCLUSION: The results of this study indicate that heparin surface modification reduces the inflammatory response to PMMA IOLs.

Adult↗
PubMed1992

Partial nucleotide sequence of poplar mosaic virus RNA confirms its classification as a carlavirus.

The nucleotide sequence of the 3'-proximal 1328 nucleotides of poplar mosaic virus (PMV) was determined and shown to contain two large open reading frames (ORFs). The ORF nearer to the 3' terminus of the RNA is capable of encoding a polypeptide of 14K with a 'zinc-finger' motif, and is homologous to sequences in corresponding positions in five other carlaviruses. The other ORF encodes a protein of 36K which includes two sequences of amino acids identified in tryptic digests as virion capsid protein, and has amino acid sequences in common with both carlaviruses and potexviruses.

Amino Acid Sequence↗
PubMed1992

Conditions accounting for substantial time spent in hospital in children aged 1-14 years.

To identify the clinical conditions associated with substantial time spent in hospital by children aged 1-14 years, records of children admitted to hospital in 1975, 1979, and 1984 were studied. Analysis was by linkage of abstracts of routine records of hospital inpatient care in six districts in southern England covered by the Oxford record linkage study. The total time spend in hospital in the acute specialties each year was calculated by summing the lengths of stay of all episodes of care for each child in each year. First, admissions with long median times in hospital per child admitted were identified. These included, notably, fracture of femur and, in the later years, leukaemia, other malignant neoplasms, and congenital disorders of metabolism. Second conditions were identified which accounted for large numbers of children with lengths of stay of five days or more. These included, in particular, congenital anomalies, asthma, and appendicitis. Third, conditions were identified which accounted for the largest numbers of bed days used. These included congenital anomalies, hypertrophy of tonsils and adenoids, asthma, otitis media, appendicitis, and head injury. Median time spent in hospital per child admitted declined for most conditions but increased for leukaemia, other malignant neoplasms, and congenital disorders of metabolism. Admission rates for children who spent five days or more in hospital each year declined for all common conditions except asthma which increased. Total numbers of beds used increased for asthma and otitis media but declined for all other common conditions.

Adolescent↗
PubMed1992

Recording of deaths in hospital information systems: implications for audit and outcome studies.

STUDY OBJECTIVE: The aim was to report on the extent to which death certificates which specify that death occurred in hospital can be matched and linked with routine hospital inpatient information systems. DESIGN: The study involved linkage of hospital records which specified that death occurred in hospital to corresponding death certificates; and linkage of death certificates which specified that death occurred in hospital to corresponding hospital records. SETTING: Six health districts in southern England covered by medical record linkage. SUBJECTS: Records were examined of patients aged 65 years and over, which specified that death occurred in hospital between 1979 and 1985. MAIN RESULTS: 98.2% of hospital record abstracts which specified that death occurred in hospital were linked by our standard computer-based techniques to death certificates. Conversely, however, only 94.4% of death certificates which specified that death occurred in hospital could be linked to the abstracts of corresponding hospital inpatient records. A major factor contributing to the latter failures may be a difference of definition of what constitutes a death "following hospital admission" in patients who die shortly after arrival at hospital. CONCLUSIONS: Linkage of hospital records to death certificates is both feasible and desirable. Error rates are generally small; but hospital inpatient record abstracts corresponding to death certificates for deaths in hospital may not invariably exist when death occurs shortly after the arrival of the patient at hospital.

Death Certificates↗
PubMed1992

Possible association of benzalkonium chloride in nebulizer solutions with respiratory arrest.

OBJECTIVE: To report a case of possible association of benzalkonium chloride in nebulizer solutions with respiratory arrest and to review the involvement of various preservative agents in paradoxical bronchoconstrictive reactions. DATA SOURCES: Reference articles, case reports, and editorials are identified in the text. DATA SYNTHESIS: Many pharmacologic agents are available for nebulization. In addition to the active drug, these nebulizer solutions may contain preservatives. We describe a case of respiratory arrest in a 64-year-old man following nebulization therapy with albuterol and ipratropium solutions. These solutions contain benzalkonium chloride as a preservative. We are aware of only one report describing two deaths associated with such a severe reaction attributable to nebulization therapy. However, many reports of milder paradoxical bronchoconstriction are available in the medical literature. CONCLUSIONS: Clinicians should be aware of the possibility of paradoxical bronchoconstrictive reactions when patients are treated with nebulized bronchodilators.

Benzalkonium Compounds↗
PubMed1992

Studies of the molecular biology of parathyroid hormone-like peptide.

Molecular biology techniques have been used to examine alternative splicing of the PLP gene, interspecies homology of PLP, the genetic relationship of PLP and PTH. Molecular biology approaches can also be successfully employed to examine both the regulation of PLP production and its function both in emulating PTH and in non PTH-related actions.

Animals↗
PubMed1992

Effect of ritanserin, a highly selective 5-HT2 receptor antagonist, on Parkinson's disease.

There is both experimental and clinical evidence to suggest a role for 5-hydroxytryptamine (5-HT) in Parkinson's disease. The effect of ritanserin, a highly selective 5-HT2 receptor antagonist, on Parkinsonian symptomatology was investigated in 10 patients in a single-blind placebo-controlled study. Akinesia and gait improved significantly in a dose-dependent manner in 5 and 7 patients respectively. However there was no significant improvement in tremor. The effects of ritanserin on akinesia and gait are consistent with a role for 5-HT in Parkinson's disease.

Aged↗
PubMed1992

Time spent in hospital by children as a health care indicator: inter-district comparisons.

It has been widely recommended that children should be admitted to hospital only if treatment cannot be provided at home, and that durations of hospital stay should be minimized. We have used record linkage to calculate a statistic which is not yet commonly available, the total time spent in hospital by children per year, and have compared this between six districts in the Oxford Region. Hospitalization rates for children who stayed a total of two days or less per year in hospital increased over time; rates for children who stayed more than two days declined. Mean and median total days spent in hospital varied between districts but, in absolute terms, the differences were small at less than one day's difference between districts per year per child admitted. Inter-district variation decreased over time, although the variation in use of day case care which remained suggests that some districts could still do more work in this fashion.

Adolescent↗
PubMed1992

Time spent in hospital by the elderly in the final year of life as a health care indicator: inter-district comparisons.

We have studied the amount of time spent in hospital by elderly people in their final year of life in 1976, 1981 and 1986 in six districts covered by the Oxford record linkage study to determine the extent of differences between districts. There was consistent but insubstantial variation between the districts. Variation declined over time, suggesting that the use of hospital care for the elderly may, in this respect, be nearing consensus. We conclude that the measure of total time spent in hospital by the elderly in their last year of life was not a powerful discriminator between districts in this region. When record linkage is implemented elsewhere in England, it will be possible to make wider geographical comparisons to determine whether important variations exist elsewhere.

Aged↗
PubMed1991

Dysregulation of parathyroid hormone-like peptide expression and secretion in a keratinocyte model of tumor progression.

Using a human keratinocyte model of tumor progression, we have examined the regulation of gene expression and secretion of a parathyroid hormone-like peptide (PLP) that has been implicated in the pathogenesis of hypercalcemia in cancer. A rapid and transient induction of PLP mRNA in response to serum stimulation was demonstrated in both established (HPK1A) and malignant (HPK1A-ras) cells; however the dose dependent increases were greater in HPK1A than in HPK1A-ras. Significant inhibition of this induction was noted with the addition of 1,25-dihydroxyvitamin D3 at a lower concentration in HPK1A than in HPK1A-ras. Amino-terminal PLP immunoreactivity and bioactivity correlated well (r = 0.98) when measured in conditioned medium. In the absence of mitogenic stimuli, malignant keratinocytes (HPK1A-ras) secreted significantly more PLP than established (HPK1A) keratinocytes. However, in response to increasing concentrations of epidermal growth factor and fetal bovine serum, PLP release was far greater from HPK1A (maximum 13 x basal) than from HPK1A-ras (maximum 3 x basal) cells. In addition, 1,25-dihydroxyvitamin D3 was more effective in inhibiting both basal and stimulated PLP secretion in HPK1A than in HPK1A-ras cultures. Reduction of extracellular Ca2+ from 2.0 mM to 0.5 mM appeared to be more effective at an early time point in reducing PLP secretion from the established cells compared with the malignant cells. These studies therefore demonstrate a progressive dysregulation of PLP expression and secretion in human keratinocytes in the transformation from established to malignant phenotype and may have important implications for understanding the pathogenetic mechanisms involved in vivo in the development of hypercalcemia in cancer.

Blotting, Northern↗
PubMed1991

Accelerated silicosis in Scottish stonemasons.

A small group of stonemasons working with sandstone was exposed to levels of respirable quartz up to 130 times the workplace standard over a period of up to 6 years. Two died of accelerated silicosis, a disease that caused serious diagnostic difficulties and was initially not recognised by the doctors of the then Department of Health and Social Security Medical Boarding Centre (respiratory diseases). Previous descriptions of this disease in the UK date back to the years of the industrial revolution (late 18th century). One other mason on the site proved to have an earlier stage of accelerated silicosis and two had radiographic changes of early classic silicosis. Regulations intended to prevent silicosis have been in place in the UK for many decades and were strengthened by the Health and Safety at Work Act in 1974. Although the workers had been aware of a health risk from quartz, they had not been able to persuade management to take effective preventive action until serious illness had occurred. Current pressures on management to cut overheads and to achieve maximum productivity could, as in this instance, lead to neglect of health and safety standards.

Adult↗
PubMed1991

Characterisation of virulent and benign strains of Bacteroides nodosus.

The extracellular proteases of 395 isolates of B. nodosus from ovine, bovine and caprine foot lesions were classified as either thermostable or thermolabile. Stable protease was associated with one and unstable protease with four distinctive isoenzyme patterns, each pattern differentiated by the relative mobility of paired isoenzymes. Pathogenicity tests on 64 isolates showed a correlation between the production of stable protease and the production of virulent ovine footrot lesions. The mean values for total protease activity, twitching motility and colony diameter were significantly higher for virulent compared to benign isolates, but the range of values overlapped. SDS-PAGE whole-cell electrophoretic profiles of virulent isolates were similar to the profiles of some benign isolates.

Analysis of Variance↗
PubMed1991

Ophthalmology in the Oxford region: analysis of time trends from linked statistics.

OBJECTIVES: to report on trends in ophthalmology workload using linked statistical data; DESIGN: analysis of linked abstracts of hospital inpatient and day case records for ophthalmology; SETTING: six districts in Southern England covered by the Oxford record linkage study; SUBJECTS: records for hospital admissions to ophthalmology from 1975 to 1985; MEASUREMENTS AND MAIN RESULTS: Over the period of study, the number of episodes of inpatient and day case care increased by 16.3%. Notable increases in age-specific admission rates were seen among the elderly. An increase in the number of individuals treated contributed about 67% and an increase in multiple admissions per individual contributed about 33% to the increase in admission rates. Both average length of stay per episode and total time in hospital per individual decreased consistently during the 11 years; and there was no increase in emergency readmissions over time. No significant changes over time were found in admission rates for retinal detachments and defects or for glaucoma. There was a statistically significant increase averaging 4.8% per annum in admission rates for cataract, and a significant decrease averaging 5.2% per annum in admission rates for strabismus and other disorders of binocular eye movement between 1975 and 1985. CONCLUSIONS: Age-specific admission rates in ophthalmology are much higher in the very young and old than in other age groups. Patterns of work in the specialty are therefore particularly affected by variation in the age distribution of the population. The increase in cataract surgery reflected both the increase in numbers of old people in the population and an increase in age-specific operation rates for cataract. Attempts to alter attitudes and behaviour of the elderly regarding eye diseases, disability, and facilities for treatment may have had a positive impact on the use of services. The decrease in admissions for children probably reflects the impact made by child health surveillance programmes. As the child screening programme has expanded, the admission rates for strabismus have decreased.

Adolescent↗