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Biomedical subjects

I Russell

Publications and source records attributed to I Russell.

At least 73 records · Page 4Linked to original sources

Antenatal cystic fibrosis carrier screening--whether, when and how?

Population screening for carriers of cystic fibrosis (CF) is now possible. Such screening may have both advantages and disadvantages and hence must be evaluated before it becomes routine practice. As the potential benefits of screening are wide and the drawbacks may include psychological effects, a combination of approaches is needed to assess screening thoroughly instead of only counting numbers of terminations or carrier tests. We describe the issues concerned and our methodology for a rigorous evaluation of population antenatal carrier screening for cystic fibrosis.

Anxiety↗

Mammographic follow up: a vital component of breast cancer management.

Women with proven breast cancer are at high risk for development of a second breast malignancy or a recurrence. An important component of clinical care is regular mammographic follow up, to enable preclinical diagnosis and avoid delay in treatment. One hundred and forty-two women with previous breast cancer attended a pilot mammographic screening program. Eleven had suspicious mammographic lesions, all clinically occult; nine breast cancers were diagnosed (two recurrences and seven new tumours). The cancer detection rate in this high-risk group of women was 6.3%, compared with 0.8% in 16,283 women screened with no history of breast cancer. Examination of the mammographic history of the 142 women showed that mammography was used infrequently as part of their clinical surveillance, and this led to a delay in diagnosis of the new or recurrent cancer. Recommendations for an appropriate regimen for use of mammography in new and established cases of breast cancer are made.

Aged↗

Thiamine secretion in yeast.

To isolate thiamine excretors and (or) overproducers, 188 cultures belonging to nine yeast and three fungal genera were screened. Nine excreted thiamine as determined by both the presence of cross-feeding zones on a thiamine-free agar medium seeded with a thiamine-requiring yeast strain and by the direct detection of excreted thiamine on agar plates. Several of these cultures produced several-fold more intracellular thiamine than the general culture population. Thiamine-requiring strains of Saccharomyces cerevisiae and S. uvarum (carlsbergensis) were identified and were tentatively assigned to 10 complementation groups.

Extracellular Space↗

Expression and regulation of glucoamylase from the yeast Schwanniomyces castellii.

Expression of the 146-kilodalton (kDa) extracellular glucoamylase by the budding yeast Schwanniomyces castellii is induced by maltose and starch. By use of antiglucoamylase antisera, we found that this expression was regulated at the level of the mRNA, taking place within 30 min after exposure of yeast cells to the respective sugars. Polyacrylamide gel electrophoresis analysis of the in vitro-translated products of total RNA from maltose-treated cells established that the glucoamylase precursor was approximately 120 kDa in size. Stable glucoamylase transcript was not produced in cells exposed to glucose, 2-deoxyglucose, and heat shock. Cells exposed to these two sugars also degraded intracellular and extracellular glucoamylase. In the presence of sugars such as cellobiose, galactose, lactose, and xylose or in the absence of any carbohydrate, a low-level, constitutive-like expression of this preglucoamylase occurred. The nascent glucoamylase underwent at least two posttranslational modifications, resulting in a 138-kDa cell-associated form and the 146-kDa active form that was found free in the medium. These results suggest that glucoamylase expression is tightly regulated similarly to expression of the enzymes responsible for maltose metabolism in Saccharomyces yeasts.

Blotting, Western↗

A study of ethanol tolerance in yeast.

The ethanol tolerance of yeast and other microorganisms has remained a controversial area despite the many years of study. The complex inhibition mechanism of ethanol and the lack of a universally accepted definition and method to measure ethanol tolerance have been prime reasons for the controversy. A number of factors such as plasma membrane composition, media composition, mode of substrate feeding, osmotic pressure, temperature, intracellular ethanol accumulation, and byproduct formation have been shown to influence the ethanol tolerance of yeast. Media composition was found to have a profound effect upon the ability of a yeast strain to ferment concentrated substrates (high osmotic pressure) and to ferment at higher temperatures. Supplementation with peptone-yeast extract, magnesium, or potassium salts has a significant and positive effect upon overall fermentation rates. An intracellular accumulation of ethanol was observed during the early stages of fermentation. As fermentation proceeds, the intracellular and extracellular ethanol concentrations become similar. In addition, increases in osmotic pressure are associated with increased intracellular accumulation of ethanol. However, it was observed that nutrient limitation, not increased intracellular accumulation of ethanol, is responsible to some extent for the decreases in growth and fermentation activity of yeast cells at higher osmotic pressure and temperature.

Biotechnology↗

Applicability of yeast extracellular proteinases in brewing: physiological and biochemical aspects.

A general screening survey for expression of extracellular acid proteinase production was performed on over 100 cultures belonging to the genus Saccharomyces. Although two strains of Saccharomyces cerevisiae showed positive extracellular proteinase phenotypes in plate tests, it was not possible to demonstrate proteolytic activities in cell-free culture supernatants in assays performed at beer pH values. Of several yeasts from other genera examined, Saccharomycopsis fibuligera and Torulopsis magnoliae produced extracellular proteinases with desirable properties. Proteolytic activities were detected in assays performed at beer pH values and at lower temperature. Brewer's wort served as a highly inducing medium for extracellular proteinase production, with T. magnoliae yielding enzyme of highest specific activity. In fact, commencement of enzyme production was detected shortly after the onset of exponential growth in brewer's wort. Inclusion of crude enzyme preparations in brewer's wort inoculated simultaneously with brewer's yeast reduced final ethanol yields slightly and was found to be effective in reducing chill haze formation in bottled beer.

Journal Article↗

Prognostic significance of tumor grade in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis.

The prognostic significance of histologic tumor grade has been evaluated in 1537 women entered into the Ludwig Trials I-IV of adjuvant therapy for node-positive breast cancer. Tumor grade was determined on histologic review of primary tumor sections by two central review pathologists using a modification of the Bloom and Richardson grading system. The 5-year overall survival rates (+/- SE) were: Grade 1, 86% +/- 2; Grade 2, 70% +/- 2; and Grade 3, 57% +/- 2 (P less than 0.0001). This survival difference was seen in both premenopausal (P less than 0.0001) and postmenopausal (P less than 0.0001) women. Significant differences in disease-free survival (DFS) by tumor grade were also observed (P less than 0.0001). The tumor grade determined by the 75 contributing local clinic pathologists was also highly significant for predicting DFS and overall survival. Tumor grade remained a statistically significant prognostic factor for DFS (P less than 0.0001) and overall survival (P less than 0.0001) in multivariate analyses controlling for nodal status, tumor size, estrogen receptor status, menopausal status, age, peritumoral vessel invasion, and treatment assigned. In postmenopausal patients for whom adjuvant treatment was compared with no adjuvant therapy, the prognostic significance of tumor grade was modified by the effect of treatment. The presence of vessel invasion by primary tumor cells was a stronger predictor of early recurrence than was increasing tumor grade in postmenopausal patients who received no adjuvant therapy. The higher failure rates for patients with high-grade tumors was due to a larger number of failures in regional and visceral sites. Tumor grade can be determined by any pathologist and allows for selection of a subpopulation of breast cancer patients at high risk for early mortality.

Adult↗

Prognostic significance of peritumoral vessel invasion in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis.

To assess the prognostic significance of peritumoral vessel invasion, data were examined for 1,510 women entered into the Ludwig Breast Cancer Group Trials I to IV evaluating adjuvant therapy for operable breast cancer with axillary nodal metastasis. Vessel invasion by tumor cells was identified by routine light microscopy in 59 per cent (889 of 1,510) of the patients and was equally distributed between premenopausal/perimenopausal (60 per cent, 468 of 778) and postmenopausal (58 per cent, 421 of 732) women. In logrank analyses stratified by nodal status (one to three or four or more positive nodes), the four-year disease-free survival (DFS) rate was significantly lower in patients with vessel invasion than in women without vessel invasion (50 per cent versus 65 per cent, P less than 0.0001). This DFS difference was seen for both premenopausal/perimenopausal (P = 0.0004) and postmenopausal (P = 0.0002) patients. The four-year overall survival rate was also lower in patients with vessel invasion (71 per cent versus 82 per cent, P = 0.0006), both for premenopausal/perimenopausal (P = 0.002) and postmenopausal (P = 0.04) women. The presence of vessel invasion was significantly associated with increasing numbers of positive axillary lymph nodes, rising tumor grade, nonstellate tumor border growth pattern, and higher steroid hormone receptor content of the primary tumor. The assessment of peritumoral vessel invasion continued to have prognostic significance for DFS (P less than 0.0001) and overall survival (P = 0.003) when evaluated in multivariate models controlling for treatment assigned, nodal status, tumor size, estrogen receptor status, menopausal status, and age. Depending on the subpopulation, patients with vessel invasion had a 41 per cent to 54 per cent greater risk of treatment failure than those without vessel invasion and a 29 per cent to 64 per cent greater risk of death. The percentage of treatment failures at distant sites was higher for women with than for those without vessel invasion (27 per cent versus 18 per cent, P = 0.003). In patients with axillary lymph node metastases, peritumoral vessel invasion may be a sign of increased systemic disease burden.

Aged↗

Mitoxantrone treatment in advanced breast cancer.

Half of our patients presenting with breast cancer will eventually require cytotoxic chemotherapy. In searching for an effective drug with low toxicity, many new drugs have been investigated. Seventeen patients with advanced breast cancer were treated with mitoxantrone, an analogue of adriamycin. The response rate was 44% (CR 6% + PR 38%). Side effects were fewer than those normally anticipated for most cytotoxic chemotherapy in that only two patients suffered hair loss and three nausea and vomiting. There was, however, significant bone marrow depression with granulocytopenia and two patients died of septicaemia following treatment. Cardiac toxicity occurred in two patients: of these, both had prior treatment with adriamycin, and one had prior radiotherapy to the chest wall. Both of these patients died.

Adult↗

Factors influencing the feeding of first-born infants.

Influences on the choice and use of an infant feeding method by primigravidae were studied from late pregnancy until six months after delivery. Data were collected by home interviews and postal questionnaires, and from hospital case-notes. Three-quarters of the women had chosen a method before their first hospital visit and most adhered to their choice. Mothers named midwives and health visitors more often than other health professionals as appropriate for discussions about feeding. However, there was little evidence of the influence of health professionals apart from an association between hospital feeding practices and duration of breast feeding. The major influences on mothers were socio-cultural. Findings suggest that breast feeding can be encouraged by a wide dissemination of information, by enabling mothers to discuss feeding with their preferred professional, by respecting an early choice of method, and by encouraging demand feeding which should begin soon after delivery.

Attitude↗