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Biomedical subjects

D Saunders

Publications and source records attributed to D Saunders.

27 records · Page 2Linked to original sources

The use of a human endometrial carcinoma cell line (RL-95) for in vitro testing of chemotherapeutic agents.

RL-95, a moderately well-differentiated adenosquamous endometrial carcinoma cell line, can be used as a model for testing chemotherapeutic agents in vitro. Cells are grown in T-75 flasks, transferred to scintillation vials, and grown for 24 hr. Following this, medium is removed and new medium containing Adriamycin (Adr) and cis-platinum (CP) is added. Effects of the two drugs are measured by cell counts and DNA synthesis. To measure DNA synthesis, cells are incubated with [3H]thymidine (3H-THY) for up to 24 hr. Decreased DNA synthesis is reflected in decreased 3H-THY uptake. Cell kill is obtained with levels of drugs that are clinically achievable. Evidence is presented for increased cytotoxicity with concomitant, rather than sequential, chemotherapy. Results are also confirmed by testing the agent on MCF-7, a well-known breast cancer cell line. The results indicate that (1) endometrial carcinoma responds to Adriamycin and cis-platinum chemotherapeutic agents in vitro, and (2) RL-95 can be used as a model for testing varying concentrations, time of exposure, and combinations of chemotherapeutic agents.

Adenocarcinoma

Changes in cerebral blood flow during anaesthesia and surgery in the sitting position.

Serial measurements of global cerebral blood flow (CBF) were made in 15 patients undergoing elective neurosurgical procedures in the sitting position, using a modified intravenous 133Xenon technique. The mean supine CBF rose from 43 (+/-3) ml/100g/min to 62 (+/-6) ml/100g/min in the sitting position and remained elevated at the end of surgery at 62 (+/-5) ml/100g/min. Both increases in CBF were statistically significant with respect to baseline supine values.

Adult

Recognition of covalent insulin-receptor complexes on viable adipocytes by anti-insulin antibodies.

Isolated rat adipocytes were photo-affinity-labelled with B2-(4-azido-2-nitrophenylacetyl)-des-PheB1-insulin or B29-(4-azido-2-nitrophenylacetyl)insulin. Four anti-insulin antibodies (3 monoclonal, 1 polyclonal) were tested for their ability to inhibit the persistent stimulation of lipogenesis caused by the covalently bound insulin [Brandenburg et al. (1980) Nature (London) 286, 821-822]. The polyclonal and 2 monoclonal antibodies, directed against the C-terminus of the B-chain, gave a significant depression, while one antibody, directed against the region A(8-10), was without effect. Under reversible conditions, without irradiation, all antibodies completely inhibited lipogenesis. For the polyclonal antibody this is shown in a dose-dependent way. It is concluded that the effective antibodies can recognize their epitope because it is accessible on the surface of the complex and does not represent part of the receptor-binding surface of insulin. This binding leads to interference with the generation and/or transmittance of the biological signal.

Adipose Tissue

Herpes simplex virus-stimulated gamma-interferon production by newborn mononuclear cells.

Blood mononuclear cells from newborns and from adults, immune or nonimmune to herpes simplex virus, were cultured with IL 2 and herpes simplex virus and the amount of gamma-interferon in the supernatant measured after 3 days. The newborn and nonimmune adult cells made equivalent trace amounts of gamma-interferon in cultures containing either herpes simplex virus or IL 2 alone and there was a 5- to 10-fold increase in cultures containing both. Experiments in which the Leu 11+ cells were either depleted or enriched suggest that this subset of natural killer cells is both necessary and sufficient for gamma-interferon production in the absence of immune T cells.

Adult

Structure-function relationships of shortened [LeuB25]insulins, semisynthetic analogues of a mutant human insulin.

Replacement of B25-phenylalanine by leucine in the insulin sequence causes marked inactivation. The effect of this sequence variation was studied here in des-(B26-30)-insulin. [LeuB25]des-(B26-30)-insulin and its B25-amide were prepared by trypsin-mediated semisynthesis from N-terminally protected des-(B23-30)-insulin and synthetic tripeptides. The relative lipogenic potency in isolated rat adipocytes was 8.0% for the truncated analogue with a free B25-carboxyl function, and 18.1% for the amidated analogue. Binding to cultured human IM-9 lymphocytes was 4% and 9%, respectively. Thus, both shortened insulins are markedly more active than [LeuB25]insulin. The PheB25----LeuB25 substitution in both the shortened and the full sequence has a moderate effect on the CD spectrum, indicating that the gross main chain conformation is largely retained in both molecules. Independent of the substitution an absolute increase of the circular dichroism is observed upon amidation of the B25-carboxyl group.

Adipose Tissue

A shortened insulin with full in vitro potency.

Des[(B26-30)-pentapeptide]insulin-B25-amide was prepared from protected des-[(B23-30)-octapeptide]insulin (pig) and H-Gly-Phe-Phe-NH2 by trypsin-mediated semisynthesis in a yield of 9% (based on insulin). The analogue was characterized with respect to chemistry, biological function and CD spectroscopy. While des[(B26-30)-pentapeptide]insulin with free carboxylate group exhibited a typical insulin activity of only 25% in vitro, des[(B26-30)-pentapeptide]insulinamide was fully active. Therefore des[(B26-30)-pentapeptide]insulin meets all structural and dynamic requirements for recognition and binding of the receptor as well as exertion of the biological effect, provided that the negative charge in the hydrophobic environment of PheB25 is neutralized.

Adipose Tissue

Life stresses and depression in the menopause.

Research on the climacteric has largely concentrated on relationships between ovarian insufficiency, oestrogen deficiency, and climacteric symptoms. Little attention has been paid to those who have no symptoms. It is proposed, in addition to these relationships, that the life events of this period are significantly involved; and that resultant stress may contribute to oestrogen deficiency as opposed to physiologically normal postmenopausal oestrogen levels. In this preliminary study, two groups of women under conditions of relatively low stress and high stress were tested over a period of 15 mth. They were rated on the Hamilton Rating Scale for depression and anxiety and results were compared with the corresponding total urinary oestrogen output. The results, which suggest a significant relationship between stress related to depression and oestrogen levels in the menopause, are discussed and compared with differing life circumstances of the subjects.

Anxiety

The re-estimation of absorbed doses of less than 1 rad measured with lithium fluoride thermoluminescent dosemeters.

The technique of ultraviolet light bleaching for the re-estimation of the absorbed dose of radiation received by lithium fluoride thermoluminescence dosemeters has been extended to the extruded ribbon and PTFE disc form of dosemeter. The threshold of detection for the re-estimation of absorbed dose was found to be 1-1 rad for the PTFE disc dosemeters and 2-8 rad for the extruded ribbon dosemeters. A further study of this technique has revealed that by raising the temperature of the dosemeter during bleaching the threshold for re-estimated absorbed doses may be substantially reduced. The optimum temperature was found to be 80 degrees C and the practical threshold for the re-estimation of absorbed dose using a PTFE disc dosemeter was determined as 750 mrad.

Evaluation Studies as Topic