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Biomedical subjects

M Baum

Publications and source records attributed to M Baum.

At least 181 records · Page 10Linked to original sources

RNase P from a photosynthetic organelle contains an RNA homologous to the cyanobacterial counterpart.

RNase P is a ribonucleoprotein enzyme in all organisms and organelles investigated so far, with the exception of chloroplasts where no enzyme-associated RNA has been detected to date. As an approach to answer the question whether an RNA component is present in RNase P from photosynthetic organelles, we have used a phylogenetically oriented strategy and searched for RNase P RNA in a postulated intermediate in plastid evolution, the cyanelle of Cyanophora paradoxa. We have detected a 351 nucleotide long RNA similar to cyanobacterial RNase P RNAs, with a proposed secondary structure that closely resembles a bacterial consensus. The RNA is encoded on the cyanelle genome and copurifies with enzyme activity. The RNA is not catalytically active by itself, but the activity of the cyanelle RNase P holoenzyme is destroyed by nuclease treatment, indicating an essential role of the RNA. Hence cyanelle RNase P, combining properties of bacterial and eukaryotic enzymes, occupies an intermediate position in RNA enzyme evolution. The first description of an RNA component in RNase P from a photosynthetic organelle might thus be an important step towards an understanding of plastid RNase P structure and function.

Base Sequence↗

Localization and expression of the closely linked cyanelle genes for RNase P RNA and two transfer RNAs.

The genomic region encoding the RNA subunit of the cyanelle RNase P has been characterized. rnpB, which has no homologue in chloroplasts, is flanked by two tRNA genes on the complementary DNA strand. Transcriptional control elements of all three genes have been experimentally determined. Comparison of the sequenced region with the corresponding loci of chloroplast genomes from vascular plants suggests that major inversions may have led to a possible loss or severe truncation of the RNase P RNA coding region during the course of plastid evolution.

Base Sequence↗

Cytomorphology of a mixed pigmented/nonpigmented pleomorphic adenoma of the ciliary body: a diagnostic pitfall in the evaluation of intraocular tumors.

Intraoperative cytology is an alternative and sometimes preferred method to frozen section in the rapid evaluation of surgical biopsies. This report describes the cytological, histological, and immunohistochemical features of a case of mixed pigmented/nonpigmented pleomorphic adenoma of the ciliary body with clinical and morphological features reminiscent of malignant melanoma. The characteristic cyto-histomorphology of this unusual tumor and its distinguishing features from malignant melanoma are discussed.

Adenoma, Pleomorphic↗

Comparison of different modes of high-frequency ventilation in surfactant-deficient rabbits.

Various modes of high-frequency ventilation (HFV) have been developed to avoid the disadvantages of conventional mechanical ventilation. In the present study, we examined the hypothesis that high-frequency oscillation (HFO) is superior to high-frequency positive pressure ventilation (HPPV) and combined high-frequency ventilation (CHFV) in surfactant-deficient rabbits. The aim of the ventilator strategy was to adjust the mean airway pressure to 2 cm above critical opening pressure of the inflation limb of the respiratory system pressure volume (P/V) curve, achieve a normal tidal volume (VT) (5 ml/kg body weight) and apply repeated sustained inflations. We studied the effect of these HFV modes on oxygenation, lung mechanics and lung histology in 15 New Zealand White rabbits during a 6-hour experiment. Statistically, the HFO group demonstrated significantly better oxygenation (P < 0.05), lung mechanics (lung stability index: P < 0.05), and better lung tissue histology compared to the HPPV and CHFV groups. In contrast to the HPPV and CHFV groups, the P/V curves of the HFO group showed significant recovery over the 6-hour period after lavage. The lungs of the HFO-treated group had a more uniform distribution of alveoli and less overdistention than the HPPV group (P < 0.002), and less atelectasis than the CHFV group (P < 0.05). The HFO group had less lung injury than the CHFV groups (P < 0.01) and its lungs contained significantly less water than both other groups (P < 0.05). We conclude that the relationship between mean and end-expiratory pressures impacts strongly on both oxygenation and the progression of injury during HFV at the same mean airway pressures. The HFO group showed less acute lung injury than the other ventilatory groups.

Animals↗

Electroencephalogram activity, catecholamines, and lymphocyte subpopulations after resistance exercise and during regeneration.

We examined the effect in ten male sports students of 30-min resistance exercise followed by either 45-min regeneration with massage treatment on a massage bench or supine rest serving as control, on plasma catecholamine concentration, number and distribution of circulating white blood cells and central activity. Resistance exercise increased free plasma adrenaline (A) and noradrenaline (NA), whereas sulphoconjugated catecholamine concentration remained unchanged as determined by high performance liquid chromatography. Exercise induced leucocytosis and lymphocytosis measured by flow cytometry was predominantly manifested by an increase in the number of lymphocytes, monocytes, CD3+ cells, CD8+ cells and CD3- CD16/56+ cells. Computer-aided electroencephalography (EEG) revealed significant increases in absolute EEG band power. The increase was highest in alpha 2 with 51.6 (SD 40.2)% (P < 0.01), followed by beta 1 with 33.3 (SD 21.0)% (P < 0.01), alpha 1 with 31.9 (SD 25.2)% (P < 0.01), beta 2 with 30.8 (SD 26.7)% (P < 0.01), delta with 26.1 (SD 28.7)% (P < 0.05), and theta with 19.8 (SD 16.5)% (P < 0.01). All hormone and immunological variables returned to pre-exercise values 45 min after exercise with no differences between massage and control treatments. However, during regeneration differences in absolute EEG-band power were observed between massage and control treatments. In central (Cz, C3, C4) and fronto-lateral (F3, F4) electrode positions absolute beta 1 spectral power density was significantly lower during massage treatment than during control (Wilcoxon test: P < 0.01). Overall, these data demonstrated that an influence of massage treatment on deactivation characteristics could be observed in EEG measurements but not in plasma catecholamine concentration or blood lymphocytes, indicating that computer-aided topographical EEG may be a useful technique for studying activation and regeneration characteristics.

Adult↗

Role of TGF beta in the anti-estrogen response/resistance of human breast cancer.

Transforming growth factor beta (TGF beta) has potent inhibitory effects upon epithelial proliferation and malignant progression may be associated with breakdown of the autocrine and paracrine inhibitory loops in which TGF beta participates. The therapeutic effecs of anti-estrogens may be partially attributable to boosting of local endogenous levels of TGF beta. This article reviews the evidence in support of TGF beta being a proximate effector in mediation of the anti-neoplastic effects of anti-estrogens. Both the conventional estrogen receptor (ER) dependent and ER independent mechanisms of action are likely to be involved. Evidence for preferential stromal induction of TGF beta by anti-estrogens is emphasized, together with the therapeutic potential of this strategy for improving outcome in early breast cancer irrespective of ER status.

Autocrine Communication↗

Protein losses in children on continuous cycler peritoneal dialysis.

Peritoneal dialysis can result in significant protein losses through the dialysate effluent. Although protein loss in chronic ambulatory peritoneal dialysis has been examined, it has not been extensively studied in patients on continuous cycler peritoneal dialysis. Such losses can contribute to protein calorie malnutrition, especially in infants and children, many of whom are on continuous cycler peritoneal dialysis. We measured protein loss during continuous cycler peritoneal dialysis in patients ranging in age from 2 months to 18 years. There was an inverse correlation between body surface area and peritoneal protein loss, expressed both as milligrams of protein per kilogram body weight per day (P < 0.0001) and as milligrams of protein per meter square body surface area per day (P < 0.05). Peritoneal fluid protein losses in patients greater than 50 kg were similar to those previously reported in adults treated with chronic ambulatory peritoneal dialysis. In contrast, infants had nearly twofold greater peritoneal protein losses per meter square body surface area than older children weighing more than 50 kg. Such protein losses in infants impair normal growth and may contribute to permanent loss of growth potential. Infants on peritoneal dialysis require early and aggressive nutritional supplementation with higher caloric and protein intake to compensate for such dialysate protein losses and maximize growth.

Adolescent↗

Prophylactic mastectomy for genetic predisposition to breast cancer: the proband's story.

The identification of the BRCA1 gene may prove a mixed blessing in the short term. First, the demand for testing might outstrip available resources, the ethics of testing are complex and the advice to give someone who tests positive is as yet unclear. Furthermore, the psychological dynamics within such families have not yet been considered seriously. As these families might be widespread, there will inevitably be problems involving clinical genetic centres in different parts of the country, or for that matter, in different areas of the world. In this paper we provide a case report, which might be considered an adumbration of things to come. The proband in this story (a co-author) was known to have inherited a genetic predisposition to cancer. This was because her identical twin had already developed the disease and she came from a kindred with a very high probability for carrying a dominant breast cancer gene in the germ line. We describe the personal reactions of an individual woman faced with these difficult decisions, the impact on her family and the impact on the clinical genetic services in different parts of the country. Our experience could help to provide a template for the development of regional services once genetic testing for predisposition to breast cancer becomes widely available.

Adult↗

Synthesis and secretion of transforming growth factor beta isoforms by primary cultures of human breast tumour fibroblasts in vitro and their modulation by tamoxifen.

Tamoxifen may mediate its effect in early breast cancer in part via an oestrogen receptor (ER)-independent pathway by directly stimulating fibroblasts to produce the negative paracrine growth factor transforming growth factor (TGF)-beta. We have previously shown that secretion of this factor is induced 3-to 30-fold in human fetal fibroblasts in vitro, and by stromal fibroblasts in vivo following tamoxifen treatment of ER-positive and ER-negative breast cancer patients. Primary cultures of breast tumour fibroblasts have been exposed to tamoxifen for 48 h, and rates of secretion of TGF-beta 1 and TGF-beta 2 measured using a quantitative immunoassay. Fibroblast strains derived from malignant and benign tumours produced and secreted similar amounts of TGF-beta 1, but benign breast tumour fibroblasts secreted significantly higher levels of TGF-beta 2 compared with fibroblasts of malignant origin. Tamoxifen did not induce any consistent increase in TGF-beta secretion into the conditioned medium, but immunofluorescence analysis for the intracellular form of TGF-beta 1 revealed evidence of increased immunoreactive protein in tamoxifen-treated fibroblasts, which is localised to the nucleus. Therefore synthesis of TGF-beta 1 appears to be stimulated by tamoxifen, but increased secretion may be abrogated in vitro. Furthermore, using immunocytochemistry and transient transfection with an ER-responsive reporter construct, no ER was demonstrable in these fibroblasts supporting the proposed ER-independent paracrine pathway.

Antineoplastic Agents, Hormonal↗

Phase II study of continuous infusional 5-fluorouracil with epirubicin and carboplatin (instead of cisplatin) in patients with metastatic/locally advanced breast cancer (infusional ECarboF): a very active and well-tolerated outpatient regimen.

Infusional 5-fluorouracil (F) with cisplatin (C) and epirubicin (E), so-called infusional ECF, is a highly active new schedule against locally advanced or metastatic breast cancer. Cisplatin, however, is a major contributor to toxicity and usually requires inpatient treatment. In an attempt to overcome this, we have investigated the effect of substituting carboplatin for cisplatin in our original infusional ECF regimen. Fifty-two patients with metastatic (n = 36) or locally advanced/inflammatory (n = 16) breast cancer were treated with 5-fluorouracil 200 mg m-2 day-1 via a Hickman line using an ambulatory pump for for 6 months, with epirubicin 50 mg m-2 intravenously (i.v.) and carboplatin AUC5 i.v. every 4 weeks, for six courses (infusional ECarboF). The overall response rate (complete plus partial) was 81% (95% CI 67%-90%), with a complete response rate of 17% (95% CI 6-33%) in patients with metastatic disease and 56% (95% CI 30-80%) in patients with locally advanced disease. Median response duration and survival for metastatic disease was 8 and 14 months respectively, and two patients with locally advanced disease have relapsed. These results are very similar to those previously achieved with infusional ECF. Severe grade 3/4 toxicity was low. Infusional ECarboF is a highly active, well-tolerated, outpatient regimen effective against advanced/metastatic breast cancer and now warrants evaluation against conventional chemotherapy in high-risk early breast cancer.

Adult↗