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Biomedical subjects

G M Clark

Publications and source records attributed to G M Clark.

At least 109 records · Page 6Linked to original sources

The promotion of healthy eating: food availability and choice in Scottish island communities.

Communities in rural areas are in receipt of health education messages on healthy eating aimed at the population. These messages are invariably composed without regard to where people reside, and, in particular, to the availability of, and access to, foodstuffs in rural areas. In this paper the authors present data derived from a participative health needs assessment on the topic of food, diet and health. The research was conducted in a number of islands of the Western Isles of Scotland and comprised seven focus groups, 33 semi-structured interviews, one community and one policy workshop, and a final community feedback session. The needs assessment demonstrated a dichotomy between local experiences of food availability, island food cultures and the contents of healthy eating advice. As a result of the research, local people and health care professionals developed a range of activities on the topic of the traditional island diet. People noted the potentially positive elements of this diet for health but also the possibility of promoting social cohesion through the consideration of food and diet histories. In addition, lobbying at a national level was also identified as necessary to the development of a 'healthy food policy'.

Adolescent↗

Steady-state evoked potential and behavioral hearing thresholds in a group of children with absent click-evoked auditory brain stem response.

OBJECTIVE: 1) To examine the distribution of behavioral hearing thresholds in a group of children who had shown no click-evoked auditory brain stem response (ABR) at maximum presentation levels. 2) To describe the relationship between the 90 Hz steady-state evoked potential (SSEP) and behavioral thresholds in these subjects. DESIGN: A retrospective study based on clinical findings obtained from 108 infants and young children. Each of these children had shown no recordable ABR to clicks presented at maximum levels (100 dB nHL). SSEP audiograms were obtained using AM/FM tones at the octave frequencies 250 to 4000 Hz. The results of these evoked potential assessments were compared with hearing thresholds established behaviorally. RESULTS: Click-ABR assessment could not differentiate between the subjects in our sample with total hearing losses and those with useful residual hearing. Although some of the ears were anacusic, more than a quarter showed residual hearing at each of the audiometric frequencies. Furthermore, at least 10% of the behavioral thresholds at each frequency fell within the moderate/severe hearing loss range. A far closer relationship was observed between SSEP and hearing thresholds. On occasions where the SSEP was absent at maximum levels, 99.5% of the ears showed either a total loss or a behavioral threshold within 10 dB of that level. When an SSEP was obtained, the hearing threshold was typically within 5 dB of the SSEP threshold. CONCLUSION: The results suggested that in our group of selected subjects, the SSEP technique was able to assess ears with only minimal amounts of residual hearing. Where the brevity of the acoustic click limits both its frequency specificity and its presentation level, the modulated tones used for SSEP testing allow accurate, frequency-specific assessment at high presentation levels.

Acoustic Impedance Tests↗

A modification of play audiometry to assess speech discrimination ability in severe-profoundly deaf 2- to 4-year-old children.

OBJECTIVE: The aim was to develop an assessment procedure that was independent of language and speech production ability, to test speech feature discrimination in severe-profoundly deaf children 2 to 4 yr of age. DESIGN: The procedure being trialed was adapted from existing procedures. The child was required to respond with a game-like motor response to a "change" in a speech stimulus that was being presented repeatedly through a speaker. The change occurred at randomly determined times, and false alarm responses were measured during the waiting periods (while the child waited for the change). Two- to four-yr-old normally hearing children and hearing-impaired children using hearing aids and a group of 4-yr-old hearing-impaired children using cochlear implants were assessed on the task. RESULTS: More than 82% of the 3- and 4-yr-old normally hearing and hearing-impaired children were able to complete the testing for the eight speech sound contrasts within three 20 minute sessions. Fifty percent of the 2-yr-old normally hearing and hearing-impaired children were able to condition and complete the task. All of the normally hearing children who completed the task successfully discriminated all speech sound contrasts. The performance of the hearing-impaired children using hearing aids was influenced by the degree of hearing loss and the type of speech contrast being tested. Similarly, the average performance of the children using cochlear implants was better for easier contrasts such as /ba/bi/ with contrasting vowel formant cues. CONCLUSIONS: This procedure has potential for use as a reliable clinical and research tool for assessing the development of auditory discrimination ability in 2- to 4-yr-old severe-profoundly deaf children.

Audiometry, Speech↗

Effects of chronic electrical stimulation on spiral ganglion neuron survival and size in deafened kittens.

We have studied spiral ganglion cell (SGC) survival and soma size in neonatally pharmacologically deafened kittens. They were implanted with a four-electrode array in the left cochlea at 100 to 180 or more days of age. Eight animals were chronically stimulated approximately 1000 hours over approximately 60 days with charge-balanced, biphasic current pulses; three were unstimulated controls. Using three-dimensional computer-aided reconstruction of the cochlea, the SGC position and cross-sectional area were stored. SGC position was mapped to the organ of Corti by perpendicular projections, starting from the basal end. The basal region of the cochlea was divided into three 4-mm segments. SGC survival (number per 0.1 mm of the length of the organ of Corti) and soma size for stimulated cochleae were compared statistically with implanted but unstimulated cochleae. There was no evidence of an effect of electrical stimulation on SGC survival under this protocol and with this duration. On the other hand, the cell size on the stimulated side was significantly larger than the control side in the middle segment (4 to 8 mm from the basal end). SGCs undergo a reduction in size after prolonged auditory deprivation; however, these changes may be partially moderated after chronic intracochlear electrical stimulation.

Animals↗

Modulation detection interference in cochlear implant subjects.

The aim of this study was to determine whether detection thresholds for amplitude modulated signals on a single electrode were influenced by a masking modulation on a second electrode in cochlear implant users. Data were collected from four post-linguistically deafened subjects using the Cochlear Limited prosthesis. Investigated were the effects of the spatial separation between test and masker electrodes, 0 to 5 electrodes (0 to 3.75 mm), and the amount of masking modulation: 24%, 48%, 72%, and 96% above detection thresholds. Initially, modulation detection thresholds for stimulation on a single electrode without masking modulation were obtained for a set of six electrodes in the middle of the array. Modulation detection thresholds on a fixed test electrode were then obtained with unmodulated and modulated masking on a second electrode, which was one of the six electrodes in the initial study. In both studies, thresholds were measured for modulated pulse duration at the modulation frequencies of 10-200 Hz. In the first study, the shape of the detection thresholds as a function of modulation frequency, the temporal modulation transfer function, generally resembled a low-pass filter for two subjects. For the other two subjects, the functions were relatively flat across modulation frequencies. In the second study, unmodulated masking resulted in a small elevation in detection thresholds across electrodes. Modulation detection interference (MDI), the difference between thresholds for the modulated maskers and the unmodulated masker, was greater for larger amounts of masking modulation than for smaller amounts of masking modulation. For three of the four subjects, MDI was higher for smaller spatial separations between the two electrodes than for larger spatial separations suggesting that a portion of MDI may be due to overlap of neural excitation distributions produced by stimulation on two electrodes in close proximity on the array.

Auditory Threshold↗

Radiation therapy and survival in breast cancer patients with 10 or more positive axillary lymph nodes treated with mastectomy.

PURPOSE: Adjuvant loco-regional radiation (XRT) frequently is recommended after mastectomy and adjuvant systemic therapy in patients with 10 or more positive axillary lymph nodes (ALN) to reduce the high loco-regional failure rate observed in this subset. In this study, we explored the possibility that adjuvant loco-regional radiation therapy (LR-XRT) also could decrease distant failure and improve overall survival (OS) in this subset of poor-prognosis patients. PATIENTS AND METHODS: Retrospectively, 618 breast patients with 10 or more positive ALN were studied. The median follow-up time was 7.5 years. All patients received systemic adjuvant therapy and 35% also received adjuvant radiation therapy. Loco-regional failure, distant failure, and OS analyses were adjusted for age, tumor size, number of positive ALN, and estrogen receptor (ER) status using Cox regression model. RESULTS: As expected, patients had a very high risk of loco-regional and distant failure. At 5 years, 30% of patients had loco-regional failure as a first event and 54% had distant failure. Radiation dramatically reduced loco-regional failure (hazards rate ratios [RR]=0.29; 95% confidence interval [CI], 0.19 to 0.45). The adjusted 5-year loco-regional failure rate was 13% with radiation and 38% without radiation (P=.0001). Radiation also was associated with improved distant control (RR=0.75; 95% CI, 0.58 to 0.96). The adjusted 5-year distant failure rate was 48% with radiation and 58% without radiation (P=.02). OS also improved with radiation (RR=0.68; 95% CI, 0.53 to 0.85). The adjusted 5-year OS was 56% with radiation and 42% without radiation (P=.001). CONCLUSION: In this cohort of high-risk breast cancer patients, XRT was associated with less loco-regional and distant failure and improved OS. This suggests that improved loco-regional control might decrease secondary systemic spread and improve survival.

Adult↗

Enzyme-linked immunoabsorbent assay-detected p53 protein accumulation: a prognostic factor in a large breast cancer cohort.

PURPOSE: This study was designed to evaluate whether patients with an unfavorable breast cancer prognosis could be identified by p53 protein overexpression detected by a quantitative enzyme-linked immunoabsorbent assay (ELISA). PATIENTS AND METHODS: Extracts from 998 breast carcinomas were assayed for p53 protein by an ELISA that used both DO-1 monoclonal and CM-1 polyclonal antibodies. Relative risks (RRs) for cancer relapse and death after 6 years of follow-up for patients with p53-positive tumors based on different dichotomization criteria were determined by multivariate Cox regression, adjusted for patient age, tumor size, S-phase fraction, estrogen (ER) and progesterone (PR) receptor concentrations, DNA ploidy, and lymph node metastases. Disease-free (DFS) and overall (OS) survival probabilities of p53-positive and p53-negative groups, using a median cutoff, were also estimated by the Kaplan-Meier method and the log-rank test. These analyses were performed for all patients and for subgroups defined by ER status, node status, and primary postoperative treatment. RESULTS: Univariate analysis showed that p53 concentrations that exceeded the median indicated significantly increased risks for relapse (P < .01) and death (P = .02). Multivariate analyses confirmed these observations (RR = 1.40; P = .02 for DFS and RR = 1.50; P < .01 for OS) and showed trends for increasing risks for relapse (P = .02) and death (P = .06) when p53 was considered as a four-level categoric variable, and identified p53 positivity as a significant predictor of outcome in node-positive patients (RR = 1.67; P < .01 and RR = 2.10; P < .01 for DFS and OS, respectively), ER-positive patients (RR = 1.45; P = .02 and RR = 1.50; P = .01 for DFS and OS, respectively), and in patients treated with chemotherapy (RR = 1.73; P = .04 for relapse and RR = 2.04; P = .03 for death). CONCLUSION: Assessment of p53 overexpression by ELISA, easily incorporated into the routine biochemical work-up of breast tumors, may be an independent predictor of reduced survival of breast cancer patients.

Adult↗

Prognostic and predictive factors in breast cancer by immunohistochemical analysis.

Most recent decisions for breast cancer patients are made on the basis of prognostic and predictive factors. In addition to the traditional tumor/nodal/metastasis staging variables, estrogen and progesterone receptor status as assessed by biochemical ligand-binding assays are the only other factors that have been adequately validated and recommended for routine clinical use. Pathologists today, however, are evaluating estrogen and progesterone receptors almost exclusively by immunohistochemical means. Although many studies suggest that these tests might have equivalent or even superior abilities to predict patient outcome, there are important methodologic shortcomings to resolve before this technology achieves the clinical and technical validation necessary to justify its routine use. Many laboratories are also evaluating other factors for clinical use by immunohistochemical techniques, including, in particular, c-erbB-2, p53, and Ki-67 proliferation indices. Although available studies suggest that these factors might indeed be helpful in making treatment decisions, their clinical usefulness is still controversial, and, like the assessment of hormone receptors, there are important unresolved technical issues, such as how to prepare the tissue, which reagents to use and, most importantly, how to interpret the results. A few laboratories have gone to considerable effort to develop reproducible methods for evaluating these factors, and they have performed comprehensive studies demonstrating the prognostic and predictive significance of their results. Nonetheless, most laboratories offering these tests have not adequately validated them and might not even be aware of the issues needing attention. Unless laboratories validate their tests or follow the procedures of others who have, they run the risk of reporting meaningless and potentially harmful results. In the future, these and other factors will be incorporated into a prognostic index that will better reflect the biologic diversity of breast cancer and that will more accurately predict clinical outcome.

Biomarkers, Tumor↗

HER-2 expression and response to tamoxifen in estrogen receptor-positive breast cancer: a Southwest Oncology Group Study.

HER-2/neu is a growth factor receptor, the expression of which has been associated with a more aggressive breast tumor biology and resistance to some types of chemotherapy. Preliminary laboratory and clinical data have led to claims that HER-2/neu expression is also associated with resistance to tamoxifen. Therefore, to test the hypothesis that HER-2/neu expression is associated with a poorer response to tamoxifen, a shorter time to treatment failure (TTF), and worse survival in estrogen receptor (ER)-positive metastatic breast cancer, we examined 205 paraffin-embedded blocks of tumors from patients enrolled on Southwest Oncology Group 8228 for HER-2/neu expression. Tumors were ER positive (ER level > 3 fmol/mg cytosolic protein in either primary tumors or metastases), and patients had not received any prior therapy for metastatic disease. All patients were treated with daily tamoxifen. The study began in 1982, and median follow-up of patients who are still alive is now 9 years. Membrane staining for HER-2/neu was evaluated by immunohistochemistry using antibody TAB 250 and was scored according to the proportion of cells staining positive; tumors were deemed positive if > 1% of the cells stained for HER-2/neu. HER-2/neu positivity was associated with lower ER values (P = 0.04) and low bcl-2 (P = 0.01). HER-2/neu positivity was not significantly associated with response rate (negative versus positive, 57 versus 54%; P = 0.67), TTF (median, 8 versus 6 months; P = 0.15), or survival (median, 31 versus 29 months; P = 0.36). There was also no significant evidence of a progressive relationship between an increasing proportion of cells expressing HER-2/neu and a shorter TTF or survival. HER-2/neu expression in ER-positive metastatic breast cancer is not significantly associated with a poorer response to tamoxifen or a more aggressive clinical course. Earlier suggestions to the contrary may have been due to failure to rigorously exclude ER-negative tumors, which are much less likely to respond to tamoxifen and more likely to have high HER-2/neu levels.

Adult↗

Health-related quality of life following orthognathic surgery.

A randomized controlled trial was conducted to compare the effects of rigid and wire fixation on health-related quality of life following surgical mandibular advancement in patients with Class II malocclusions. Sixty-four patients randomly selected to receive rigid fixation with bicortical position screws were compared with 63 patients randomly selected to receive nonrigid fixation with inferior border wires. Quality of life was measured using the Sickness Impact Profile, a generic measure of health-related quality of life, and the Oral Health Status Questionnaire, a specific measure of oral health and function designed for use with orthognathic surgery patients. Patients were evaluated prior to application of orthodontic appliances, approximately 2 weeks before surgery, and 1 week, 8 weeks, 6 months, 1 year, and 2 years following surgery. Neither instrument revealed a statistically significant difference in quality of life between wire and rigid fixation at any time period. The health-related disability associated with Class II malocclusion is modest compared to many other medical conditions. Nonetheless, orthognathic surgery patients exhibit progressive and statistically significant improvement in health-related quality of life across a wide variety of functional domains, regardless of the fixation method used.

Adolescent↗

Heat shock proteins hsp27 and hsp70: lack of correlation with response to tamoxifen and clinical course of disease in estrogen receptor-positive metastatic breast cancer (a Southwest Oncology Group Study).

In this study, we tested the hypothesis that heat shock proteins (hsps) 27 and 70 are associated with clinical resistance to tamoxifen. hsp27 is, like progesterone receptor, an estrogen-regulated protein. hsp70 is also of interest because of its interaction with estrogen receptors and because hsp70 is a component of the molecular chaperone machinery functioning in the assembly and trafficking of steroid receptors. In addition, hsps in general help protect cells against noxious stimuli and stress, and their expression has been linked to drug resistance. The study involved 205 tumors from estrogen receptor-positive tamoxifen-treated breast cancer patients with metastatic disease. All patients received daily tamoxifen as initial therapy for metastatic disease. The study began in 1982, and follow-up is now 9 years. hsp27 and hsp70 were detected by immunohistochemistry and scored according to the nuclear and/or cytoplasmic content. Expression of hsp27 or hsp70 was unrelated to estrogen receptor content, progesterone receptor content, menopausal status, age, and presence of visceral disease. Cytoplasmic and nuclear hsp27 positivities were weakly and inversely related to each other (P = 0.05). There was a significant association between cytoplasmic hsp27 and cytoplasmic hsp70 content (P < 0.001), as well as between nuclear hsp70 and nuclear hsp27 content (P = 0.001). Cytoplasmic and nuclear hsp70 were also associated (P = 0.02). However, increased hsp27 and hsp70 expression (nuclear or cytoplasmic) was not significantly associated with response to tamoxifen, time to treatment failure, or survival. Thus, this study clarifies the lack of clinical utility of hsp27 and hsp70 in predicting the response to tamoxifen in an estrogen receptor-positive breast cancer population.

Adult↗

Prognostic value of prostate-specific antigen for women with breast cancer: a large United States cohort study.

Prostate-specific antigen (PSA) is a valuable tumor marker used for diagnosis and management of prostate cancer. Recently, PSA has been found in various female tissues and body fluids. Female breasts, both normal and abnormal, including cancerous tissues, can produce PSA, and this production is regulated by androgens and progestins. Preliminary data suggested that patients with breast tumors positive for PSA may have better prognosis compared to those with PSA-negative breast tumors. This study examines the prognostic value of PSA in a large cohort study of United States patients. Using a PSA assay that has a lower detection limit of 0.001 ng/ml, we measured PSA in tumor cytosolic extracts of 953 women with primary breast cancer. Other information available for this study included age, follow-up time, survival outcome, tumor size, nodal status, steroid hormone receptor levels, DNA analysis by flow cytometry, and postoperative treatment. The median follow-up time was 73 months. During the follow-up, 200 patients relapsed and 188 died. PSA presence was found to be significantly associated with smaller tumors, tumors with low S-phase fraction, diploid tumors, younger patient age, and tumors with lower cellularity. Survival analysis indicated that the relative risks (RRs) for relapse and death were both significantly lower [RR = 0.67 (P = 0.01) for relapse; RR = 0.72 (P = 0.05) for death] in PSA-positive patients (levels higher than the 30th percentile of PSA values) than in PSA-negative patients. The reduced risks for relapse and death remained statistically significant after other clinical and pathological variables were adjusted in the multivariate analysis [RR = 0.68 (P = 0.02) for relapse; RR = 0.65 (P = 0.02) for death]. Our results suggest that the measurement of PSA in breast tumor extracts provides additional information on the prognosis of patients with primary breast cancer.

Adult↗

Effects of major Class II occlusal corrections on temporomandibular signs and symptoms.

This study explored the relationship between malocclusion and signs and symptoms of temporomandibular disorders (TMD) in 124 patients with severe Class II malocclusion, before and 2 years after bilateral sagittal split osteotomy (BSSO). Patients were evaluated with the Craniomandibular Index (CMI), the Peer Assessment Rating Index (PAR Index, to assess gross changes in the occlusion), and symptom questionnaires. The results showed a significant improvement in occlusion; PAR Index scores dropped from a mean of 18.1 before surgery to a mean of 6.1 at 2 years postsurgery (P < 0.001). The CMI and masticatory index (MI) for muscle pain indicated clinically small but statistically significant improvement (P = 0.0001) from before surgery (mean CMI = 0.14, mean MI = 0.15) to after surgery (mean CMI = 0.10, mean MI = 0.08). The number of patients with clicking upon opening decreased significantly from 33 (26.6%) to 13 (10.5%) (P = 0.001). However, the number of patients with fine crepitus increased from 5 (4.0%) before surgery to 16 (12.9%) at 2 years postsurgery (P = 0.005). Significant reductions in subjective pain and discomfort were also found 2 years after surgery. The magnitude of change in muscular pain was not related to the severity of the pretreatment malocclusion, a finding that suggests that factors other than malocclusion may be responsible for the change in TMD.

Adolescent↗

Telomerase activity and survival of patients with node-positive breast cancer.

BACKGROUND: Shortening of telomeres (specialized structures at the ends of chromosomes) beyond a certain length may signal a cell to stop dividing and to enter senescence. A ribonucleoprotein enzyme, telomerase, is a key component in maintaining telomere length. Because the majority of cancers express telomerase but most normal somatic tissues do not, we measured the level of telomerase expression in primary breast cancer specimens for correlation with traditional prognostic indicators and disease outcome. METHODS: Telomerase activity was measured in frozen human breast cancer specimens by use of the Telomeric Repeat Amplification Protocol (TRAP) assay. The level of telomerase activity was expressed as total product generated (TPG) and was corrected for specimen cellularity by expressing it as a ratio of TPG to the sample's 28S ribosomal RNA content. RESULTS: A preliminary study of 150 breast cancer specimens demonstrated that telomerase activity correlated with the fraction of cells in S phase of the cell cycle (r(sp) = .23). In a larger prognostic study of 398 tumors from patients with lymph node-positive breast cancer, telomerase expression correlated with S-phase fraction, progesterone receptor level, DNA ploidy, and lymph node status. After correcting for sample cellularity, increasing TPG levels were associated with decreased disease-free survival (P = .041) and overall survival (P = .009) of the patients. The telomerase activity level remained strongly predictive of death (P = .027) and marginally predictive of disease recurrence (P = .08) after adjustment for other prognostic factors. All P values are two-sided. CONCLUSIONS: Telomerase activity in human breast cancers is associated with a more aggressive tumor phenotype in patients.

Adult↗

Mitosin (a new proliferation marker) correlates with clinical outcome in node-negative breast cancer.

Tumor proliferation rate is an important prognostic factor in breast cancer, and S-phase fraction (SPF), as measured by flow cytometry, is the most clinically validated of several methods for measuring it. However, flow cytometry is not well suited to evaluating the formalin-fixed, paraffin-embedded tumors that are routinely available or to the increasing number of small breast cancers. These and other limitations have motivated research into alternative methods for measuring proliferation, including immunohistochemistry (IHC) against cell cycle-related antigens, which are better suited for the evaluation of small archival tissue samples. Mitosin is a recently described 350 kD nuclear phosphoprotein that is expressed in the late G1, S, G2, and M phases of the cell cycle but not in G0. Using a new monoclonal antibody (14C10), this pilot study evaluated mitosin expression by IHC in a series of 386 node-negative, formalin-fixed, archival breast cancers and correlated the results with several prognostic factors and clinical outcome (median follow-up, 78 months; range 3-214 months). The median and range of mitosin positive cells were 7% and 1-47%, respectively. There was a strong positive correlation between mitosin and SPF (r = 0.57; P = 0.0001), and there were significant negative correlations with estrogen receptor, progesterone receptor, and patient age. Mitosin was not related to overall survival in this pilot study. However, in a univariate cutpoint analysis of disease-free survival (DFS), patients with high levels of mitosin (>9% positive cells) had significantly worse DFS than did patients with lower levels (68% versus 84% at 5 years, respectively). In a multivariate analysis of DFS, large tumor size (>2 cm) and high mitosin were the only independently significant predictors of recurrence (relative risks = 2.47 and 1.72, respectively) in a model containing the additional factors estrogen receptor, progesterone receptor, patient age, and SPF. These preliminary results suggest that mitosin as assessed by IHC may be superior to SPF as a prognostic factor in node-negative breast cancer, but additional studies are necessary to validate these promising findings.

Animals↗

Intracellular responses of the rat cochlear nucleus to sound and its role in temporal coding.

The anteroventral cochlear nucleus (AVCN), the first centre of the central auditory pathway, contains globular bushy cells, which are unique in their ability to produce fast excitatory post-synaptic potentials (EPSPs). Using in vivo intracellular recordings in the rat AVCN we examined these fast EPSPs in relation to temporal coding. At frequencies up to 2.5 kHz, EPSPs were evoked on successive sine waves of the stimulus with EPSP summation limited. This one-to-one relationship between the EPSPs and the sound wave period was present at higher frequencies and over a greater intensity range than for action potentials. These results suggest that temporal coding is possible in globular bushy neurones by their ability to extract temporal information through fast processing of convergent presynaptic input.

Acoustic Stimulation↗

Lack of prognostic value of cathepsin D levels for predicting short term outcomes of breast cancer patients.

The value of cathepsin D determinations done on tumor cytosols in evaluating the prognosis of breast cancer patients has been debated in the literature. Our previous work suggested that cathepsin D determinations were not of prognostic value, but in that study we used immunoblotting and immunohistochemical methods rather than the more widely used double antibody immunoradiometric (IRMA) assay for measuring cathepsin levels. Here we report our results determining cathepsin D using components of a commercially available IRMA system on a large patient sample (n = 1984). Reagents from a commercially available IRMA kit were used to analyze cathepsin D levels in the cytosols of 1984 patients with breast cancer. All patients had invasive breast cancer with known tumor size and with some axillary nodes pathologically examined. Only patients with T1 and T2 tumor sizes were included. Median follow-up was 37 months. The hypothesis that high cathepsin D levels correlated with poorer outcome (poorer DFS or OS) was not confirmed, either in all patients, or in node-positive or node-negative subsets. Only in patients treated with adjuvant therapy were higher cathepsin D levels correlated with negative outcome (worsened OS, but not DFS), although given the large number of subsets analyzed this correlation may be spurious. Multivariate analyses using interaction terms did not support the concept that high cathepsin D levels correlate with resistance to adjuvant therapy. In this study evaluating the value of cathepsin D using components from a kit widely used for measuring cathepsin D levels, we conclude that cathepsin D is of doubtful value in predicting risk of early relapse or death for patients with newly diagnosed invasive breast cancer.

Adult↗

LIF potentiates the NT-3-mediated survival of spiral ganglia neurones in vitro.

The survival of auditory neurones depends on the continued supply of trophic factors. Early postnatal spiral ganglion cells (SGC) in a dissociated cell culture were used as a model of auditory innervation to test the trophic factors leukaemia inhibitory factor (LIF) and neurotrophin-3 (NT-3) for their ability, individually or in combination, to promote neuronal survival. The findings suggest that LIF supports neuronal survival in a concentration-dependent manner. Moreover LIF potentiated NT-3-mediated spiral ganglion neuronal survival in a synergistic fashion.

Animals↗