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Biomedical subjects

D Henderson

Publications and source records attributed to D Henderson.

At least 181 records · Page 10Linked to original sources
PubMed1989

3H-ZK 98,734, a new 11 beta-aryl substituted antigestagen: binding characteristics to receptor and serum proteins.

Recently, in the laboratories of Schering in Germany a competitive progesterone antagonist, ZK 98,734, was synthetized, which is characterized by a similar antigestagenic activity as RU 38,486, synthezised by Roussel-Uclaf in France, as assessed by inhibition of nidation tests in rats and guinea pigs. However, this compound has a substantially lower antiglucocorticoid activity measured in cell culture systems than RU 38,486. The purpose of this study was to present a comparison of biochemical and physical properties of the complexes formed by the human uterine progesterone receptor with 3H-ZK 98,734 on one hand and with other well-established progestins on the other hand. ZK 98,734 competed in the same order of magnitude as progesterone or RU 38,486 for the 3H-R5020 binding site of progestin receptor, whereas R5020, Org 2058 or progesterone were unable to compete against 3H-ZK 98,734. This apparent contradiction could be explained by means of FPLC-chromatography and sucrose density centrifugation technique. FPLC-chromatography with an anion exchange column (Mono Q, Pharmacia, Uppsala, Sweden) showed that 3H-ZK 98,734 forms at least two stable complexes with uterine cytosol, on one hand with serum albumin, which presents almost 90% of bound radioactivity, and on the other hand with the two native progestin receptor forms, corresponding to 4S and 8S receptor forms in sucrose density gradient analysis. Competition experiments in liver cytosol of adrenalectomized rats with increasing concentrations of unlabeled ligands other than dexamethasone showed that ZK 98,734, RU 38,486 and cortisol displaced 3H-dexamethasone efficiently from the binding sites in the cytosol. Furthermore, results concerning the specificity of 3H-cortisol binding to serum proteins in diluted pregnant serum demonstrated that ZK 98,734 did not compete with 3H-cortisol for serum binding.

Animals↗
PubMed1989

Gestodene: a novel synthetic progestin--characterization of binding to receptor and serum proteins.

Gestodene, 17 alpha-ethinyl-13-ethyl-17 beta-hydroxy-4,15-gonadien-3-one, is a new orally active progestational agent, which is available for clinical use in oral contraceptives. The aim of the present study is to make a broad characterization of gestodene at the receptor level and to discuss the results in comparison to those of established progestogens. Kinetic studies of 3H-gestodene uptake show a rapid increase in the amount of specific binding during the first three hours. After saturation, the amount of specifically bound 3H-gestodene remained almost constant up to 24 hours at 4 degrees C. The dissociation of 3H-gestodene from the cytoplasmic myometrial progestone receptor, measured by displacement of labeled steroid with dextran-coated charcoal treatment at 4 degrees C at various times, showed a biphasic or two-component first order dissociation curve. As anticipated, sucrose gradient centrifugation analysis of the 3H-gestodene-labeled cytosol of human myometrial tissue showed that the gestodene binding components sedimented in the 4S and 8S region. A 200-fold molar excess of nonradioactive gestodene reduced only the 8S binding of 3H-gestodene. 4S binding of 3H-gestodene was not reduced, which indicate the existence of a second high capacity binding component. In biological test systems, such as the Clauberg test or Kaufmann test, gestodene has proved to be a very effective progestogen. Among nortestosterone derivatives it is one of the most potent and resembles progesterone biologically in its progestogenic effects. This biologically identical gestagenic activity of gestodene and progesterone is reflected by a very similar behavior in vitro in terms of binding to progesterone receptors of human uterus cytosol. Furthermore, competitive studies indicated that gestodene like other synthetic progestagens also displays some affinity for androgen and glucocorticoid receptors but no measurable affinity for the estrogen receptor. Remarkable is the high binding affinity of gestodene to the binding sites of the mineralocorticoid receptor of rat kidney with a RBA value of 350% compared to aldosterone.

Animals↗
PubMed1989

The regulation of expression of mouse mammary tumor virus DNA by steroid hormones and growth factors.

Mouse mammary tumor virus (MMTV) expression is associated with hyperplastic alveolar growth and subsequent development of mammary cancers in the mouse. The expression of this virus is also controlled by factors involved in the normal proliferation and differentiation of the mammary epithelium. During pregnancy when the mammary gland undergoes massive proliferation, MMTV expression is increased. Steroid hormones and growth factors that play an important role in the proliferation of mammary gland cells are responsible for the increased MMTV expression. In sarcomatous transformation of mouse mammary epithelial cells, MMTV expression is repressed. This repression is due to negative control of MMTV expression by transforming growth factor-beta (TGF beta). This growth factor is produced in high amounts when mammary epithelial cells progress into the transformed state. The expression of MMTV is therefore under multiple control by steroid hormones and growth factors.

Animals↗
PubMed1989

Effects of sodium salicylate on evoked-response measures of hearing.

The effects of sodium salicylate on auditory sensitivity, frequency selectivity, and temporal resolution were monitored in chinchillas using evoked responses recorded from the inferior colliculus. Administration of sodium salicylate (450 mg/kg/day for 5-15 days) resulted in serum salicylate levels of 25-50 mg/100 ml. The salicylate administration caused elevation of evoked response thresholds (up to 30 dB), mainly at the high frequencies. Frequency selectivity, as estimated by the Q10 dB value of evoked-response tuning curves, was poorer at 4 kHz during drug administration than during the no drug (control) condition. Temporal resolution, as estimated by recovery from forward masking was not significantly poorer during salicylate administration than before administration. However, there was a trend toward longer recovery in animals with large threshold shifts. These results are consistent with models suggesting that salicylate affects the auditory system at the level of the organ of Corti. They also suggest that while the changes in hearing that occur after salicylate administration are consistent with those seen in sensorineural hearing loss, the changes in hearing in the chinchilla are small enough to preclude the use of the drug as a practical model for sensorineural loss.

Animals↗
PubMed1989

Some difficulties encountered in teaching physician-parent communication in a pediatric emergency department.

In an attempt to increase physician-parent communication in cases of a child's emergency hospitalization, an informational protocol was developed with 10 topics to be discussed and checked off by the physician. Compliance was sporadic, with only 130 protocols completed during the first month, despite measures to improve its use. During the seven-month study period there were 2161 admissions, but only 466 protocols completed (21.5%). We excluded 143 forms because of errors in completion. The remaining 323 forms were analyzed for educational level of the physicians, topics omitted, patient diagnosis, and physician's rating of parent sophistication. Compliance in discussing each topic ranged from 77 to 93%. Attending physicians discussed all topics less than trainee physicians. All physicians discussed guilt feelings least (P less than 0.001). Guilt was discussed 55 and 62% of the time when the diagnosis was poisoning or chronic disease, respectively. Topics discussed were unrelated to parental sophistication. This protocol was unhelpful in improving communication.

Child↗
PubMed1988

Transport, metabolism, and DNA interaction of melphalan in lymphocytes from patients with chronic lymphocytic leukemia.

We investigated the transport of [chloroethyl-14C]melphalan with lymphocytes from three groups of patients with chronic lymphocytic leukemia (untreated, treated sensitive, and treated resistant). There was no significant difference in the Km or Vmax of melphalan transport in lymphocytes from the three groups. In addition, there were no significant differences in intracellular melphalan levels after a 35-min incubation with 5.4 microM melphalan among the three groups. There was no evidence of intracellular metabolism of melphalan to dihydroxymelphalan except in lymphocytes from one treated sensitive patient. DL-2-Aminobicyclo[2,2,1]heptane-2-carboxylic acid, a specific analogue of the sodium-independent leucine-preferring amino acid transport system, inhibited the uptake of melphalan to a greater extent in lymphocytes from resistant patients than in those of untreated patients. Glutathione levels were not significantly different in lymphocytes from resistant patients as compared to those of untreated patients. The percentage of DNA cross-links as determined by an ethidium bromide fluorescence assay was 2-5-fold greater in lymphocytes from untreated patients than in those of resistant patients. These results suggest that resistance to the nitrogen mustards in patients with chronic lymphocytic leukemia is secondary to neither a transport defect nor alteration in intracellular melphalan levels but rather due to some other mechanism responsible for decreased DNA cross-links.

Amino Acids↗
PubMed1988

Careers of dentists undertaking a medical qualification.

The careers of doubly-qualified dentists have been re-examined, 12 years after the report by Henderson, Liversedge and James (1977). Three groups of medically qualified dentists were analysed. (a) those qualifying before 1960; (b) those qualifying between 1960 and 1975; (c) those qualifying since 1975. An increased proportion of those embarking on a medical qualification fail to return to a dental career, despite a stated intention to do so. There appears to be a 'wastage' to dentistry of approximately 40% of those dentists who subsequently obtain a medical qualification. Of those who do return, most practice hospital specialties at consultant level.

Adult↗
PubMed1988

48Ti

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Journal Article↗
PubMed1988

Differing interpretations by pathologists of the pT category and grade of transitional cell cancer of the bladder.

The UICC pT category for transitional cell cancer (TCC) of the bladder was recorded as assigned from the routine service of a pathology laboratory. All reports had been passed for release after review by pathologists of the status of senior registrar or above. After 99 cases had been collected, the slides available to the original pathologist were reviewed by one dedicated pathologist in continuous session who was ignorant of the original report. No new sections were cut. There was disagreement with the original report of pT category in 14 cases: 13 were downstaged (including 6 from invasive to superficial) and 1 upstaged. There was disagreement with the original differentiation grade in 13 cases: 10 TCC were considered to be more differentiated and 3 less differentiated than the original report. A second pathologist reviewed the pT category only of 13 of the 14 cases, disagreeing with the original pT category on 8 occasions and with the pT category assigned by the dedicated pathologist on 7 occasions. These findings have important implications for advising patients on prognosis and clinical management and in the design and reporting of therapeutic trials.

Carcinoma, Transitional Cell↗
PubMed1988

Breast lumps: rare presentation of oat cell carcinoma of lung.

Two cases of oat cell carcinoma are described. Both patients presented initially with a lump in the breast. A review of the published reports on breast metastases as a presenting feature of malignant disease was performed and lung cancer was found to be the commonest extramammary tumour to present as a breast mass (80% of cases) and usually as small cell carcinoma.

Adult↗
PubMed1988

Coping with rising food costs in a closed economy: feeding behavior and nocturnal hypothermia in pigeons.

The pigeon's response to increasing fixed-ratio schedules in a 24-hr closed economy is marked by changes in feeding behavior during the daily light phase and by changes in body temperature during the dark phase. The time course of these responses to increasing behavioral cost of obtaining food is very different. Feeding is most affected immediately, within the first day of exposure to moderate fixed ratios. The number of times the pigeons produce the food hopper each day decreases, and the rate at which they eat from the food hopper (grams per minute) when it is available increases, as the fixed ratio is raised. Body temperature is affected later, falling to progressively lower resting levels during the dark phase as body weight drops at the higher fixed ratios when food intake is reduced. The changes in feeding and in body temperature that occur as the fixed-ratio schedule increases seem to reduce daily energy expenditures, within the constraints imposed by the experiment. The ascending and descending limbs of the bitonic function obtained when total daily operant responding is plotted as a function of fixed-ratio schedule in the closed economy is possibly related to the occurrence of thermoregulatory strategies for energy conservation. The energetic analysis of performances in the closed economy requires consideration of a variety of energetic strategies available to the species being studied.

Animals↗
PubMed1987

Cypermethrin pour-on for the control of ticks (Ixodes ricinus) on sheep.

Trials were carried out on 11 farms to assess the effectiveness of 2.5 per cent w/v cypermethrin pour-on for the control of ticks on sheep. Treatment at the rate of 5 ml/10 kg bodyweight gave 92 per cent control of ticks on ewes for up to nine weeks and 88 per cent control on lambs for up to eight weeks.

Administration, Topical↗
PubMed1987

The hormone response element of the mouse mammary tumour virus DNA mediates the progestin and androgen induction of transcription in the proviral long terminal repeat region.

Mouse mammary tumour virus (MMTV) gene expression has been shown to be regulated by glucocorticoids. A hormone response element (HRE) located between -202 and -59 upstream of the start of transcription in the long terminal repeat (LTR) region of the proviral DNA is required for this induction. We have investigated the role played by the HRE in the induction of MMTV LTR transcription by other classes of steroid hormones. Chimaeric constructs containing the HRE and the authentic LTR promoter linked to an indicator gene or the HRE linked to an otherwise hormone insensitive promoter directing the transcription of an indicator gene, were transfected into the human mammary tumour cell line T47D. Transcription at the MMTV LTR promoter or at the previously hormone-insensitive promoter was induced by progestins and androgens but not by oestradiol in transfected cells that contained functional receptors for these hormones. These results identify the HRE as the cis-acting element that mediates the progestin and androgen induction of MMTV LTR transcription. The HRE is therefore a DNA element that is required not just for glucocorticoid but also for progesterone and androgen induction of MMTV LTR transcription.

Acetyltransferases↗
PubMed1987

Carbohydrate residues in non-malignant prostatic epithelium as revealed by lectins.

Non-neoplastic prostatic epithelium from 39 patients obtained at transurethral resection for outflow tract obstruction and 5 normal prostates from men under 35 years of age obtained at postmortem were formalin-fixed and paraffin-embedded. The distribution of 8 lectin receptors were studied using a peroxidase anti-peroxidase method and an avidin-biotin method. Con A, WGA, and PNA bound to most epithelial cells. Con A and WGA also showed major stromal binding. Approximately 5% to 10% of cells bound UEA1, GS1, DBA, SBA and BPA. No major differences in lectin receptor expression were observed between normal and hyperplastic epithelium with either of the immunohistochemical techniques except that hyperplastic cells stained more strongly than normal epithelium.

Adult↗