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Biomedical subjects

R Mitchell

Publications and source records attributed to R Mitchell.

At least 127 records · Page 7Linked to original sources
PubMed1995

Immunometric assays of luteinizing hormone (LH): differences in recognition of plasma LH by anti-intact and beta-subunit-specific antibodies in various physiological and pathophysiological situations.

Restricted immunoreactivity of plasma luteinizing hormone (LH) has been described in some subjects when assayed with certain methods involving antibodies against intact LH. We have compared the performance of the Amerlite LH-30 (A) and Delfia LHSpec (D) assays (which include anti-intact and beta-specific antibodies, respectively) in normal and pathological conditions. As shown previously, results of the two systems were highly correlated with each other and, as we show here, with those of a bioassay. We found eight outliers (results outside the 95% confidence interval of the regression) among 427 samples studied from 121 subjects. Of the outliers, five had Delfia results in a range (< 1 IU/L) that was associated with poor assay precision for that assay, and the ratios of their values by both methods (A:D ratios) were very low. This ratio was affected by endocrine status, e.g., was lower in postmenopausal women than in premenopausal controls, and varied intraindividually within the same menstrual cycle. The restricted immunoreactivity described previously for assays involving anti-intact LH antibodies may, in part, reflect these differences, which, in turn, may reflect the presence of isoforms (e.g., glycoforms) that are differentially recognized by assays that have different antibody configurations.

Antibodies↗
PubMed1995

Coping strategies of caregivers of family members with dementia.

Data derived from a national sample of 89 caregivers of non-institutionalized family members with dementia were examined in order to identify the specific coping strategies caregivers utilized and whether the identified strategies were associated with negative or positive outcomes. Results from this study indicated that caregivers predominantly used problem-focused strategies. Further analysis demonstrated that employing more positive coping strategies did not necessarily result in a reduced sense of burden.

Adaptation, Psychological↗
PubMed1994

Proton uptake by cytochrome c oxidase on reduction and on ligand binding.

On reduction, cytochrome oxidase was found to take up 2.4 +/- 0.1 protons in the pH range 7.2-8.5, of which 2 are associated with the binuclear centre, and the remaining fractional proton with haem a/CuA. Ligation to oxidised cytochrome oxidase of the azide, formate, fluoride or cyanide anions is accompanied by uptake of one proton. In the case of the reduced enzyme, no protonation changes are observed on binding O2 (Hallén S. and Nilsson T. (1992) Biochemistry 31, 11853-11859) or CO. Cyanide binding to reduced oxidase is, in contrast, still accompanied by uptake of a proton. These findings are discussed in terms of our previously-published proposal for the ligand chemistry of the binuclear site. The results overall suggest a principle of electroneutrality of redox and ligand state changes of the binuclear centre, with charge compensations provided only by protonation reactions.

Animals↗
PubMed1994

Evidence for a role of protein kinase C in the sustained activation of rat dorsal horn neurons evoked by cutaneous mustard oil application.

The intracellular mechanisms involved in the sensitisation of spinal dorsal horn neurons brought about by sustained or repeated nociceptive inputs are unknown. The present experiments addressed any role of protein kinase (PKC) in sustained nociceptive responses of rat dorsal horn neurons by: (i) ionophoretic administration of PKC inhibitors whilst recording activity evoked by repeated cutaneous application of mustard oil; and (ii) assessing subcellular translocation of PKC evoked in spinal cord by cutaneous application of mustard oil. Both marked attenuation of mustard oil-induced neuronal activity by PKC inhibitors and selective translocation of PKC in spinal cord tissue ipsilateral to mustard oil application strongly supported a critical role of PKC in sustained nociceptive responses to mustard oil.

Administration, Cutaneous↗
PubMed1994

Oral ondansetron pharmacokinetics: the effect of chemotherapy.

The effect of a typical 5-day chemotherapy treatment with cisplatin (20-40 mg/m2 per day) and 5-fluorouracil (5-FU, 1 gm/m2 per day) on the pharmacokinetics of ondansetron was investigated. Twenty cancer patients received 8 mg of ondansetron in three periods, including an oral tablet on day 1, an intravenous infusion on day 4, and an oral tablet on day 5. Absolute bioavailability after the oral dosing on day 1 was 87.5 +/- 31.3%, and on day 5 was 85.2 +/- 22.1% (P > .05). Mean values of AUC, Cmax, Tmax, and half life on days 1 and 5 were 399 +/- 275 and 381 +/- 222 ng.hour/mL, 53.3 +/- 26.8 and 43.6 +/- 21.7 ng/mL, 1.9 +/- 1.4 and 2 +/- 1.4 hours, and 5.21 +/- 1.78 and 6.19 +/- 1.99 hours, respectively. These values were not significantly different (P > .05). In summary, this study showed that cisplatin and 5-FU did not significantly alter the pharmacokinetics of oral ondansetron in cancer patients during the 5 days of chemotherapy. Oral bioavailability of ondansetron appeared to be greater in cancer patients than in healthy subjects.

Administration, Oral↗
PubMed1994

Evidence for a role of metabotropic glutamate receptors in sustained nociceptive inputs to rat dorsal horn neurons.

Several antagonists at metabotropic glutamate (mGlu) receptors, when applied ionophoretically, inhibited the excitation of single dorsal horn neurons elicited by cutaneous administration of the C fibre-selective algogen, mustard oil. The selectivity and stereospecificity of AP3 isomers at mGlu, compared to NMDA receptors was confirmed on responses to agonists and matched by their effects on mustard oil-evoked activity.

Animals↗
PubMed1994

Smoking, alcohol and oral cancer in south east Scotland: a 10-year experience.

OBJECTIVE: To examine the relationship of oral carcinoma to tobacco and alcohol consumption in patients referred over a 10-year period. DESIGN: Analysis of records obtained for the age of presentation, the tobacco and alcohol intake, the site and type of carcinoma. SETTING: All patients with carcinoma of the mouth and associated structures referred to the Joint Onocology/Maxillofacial Clinic at Edinburgh Royal Infirmary by General Medical and Dental Practitioners together with hospitals and hospital departments within South East Scotland. SUBJECTS: A total of 454 patients, with a mean age of presentation for males of 63.8 years, for females 68.0 years. RESULTS: 58% of those with carcinoma had a smoking history, with 24% drinking more than 20 units of alcohol per week. 60% of patients with oral tumours smoked. The tongue and floor of mouth were the most common sites, and over 95% of tumours here were squamous cell carcinoma. A high proportion of patients with floor of mouth tumours had a smoking history (79%) with a higher than average alcohol consumption (41% drank over 20 units). CONCLUSION: It is suggested that these two carcinogens, smoking and alcohol, could be site specific in the oral cavity, and have an additive role. In public health terms the Scottish people need to reduce the intake of both in order to adequately reduce their risk of having oral carcinomas.

Adolescent↗
PubMed1994

Maintenance of identical p53 mutations throughout progression of squamous cell carcinomas of the tongue.

The occurrence of mutations within the coding sequence of the p53 tumour suppressor gene is now well documented for squamous cell carcinomas of the head and neck region. However, evidence that these mutations are required for the maintenance and progression of squamous tumours is still formally lacking. To test this we have examined whether p53 mutations detected in primary squamous cell carcinomas of the tongue are also detected in the corresponding lymph node metastases. Three different p53 mutations were detected in each of three primary tongue squamous cell carcinomas (SCC), and in each case the same mutation was detected in a lymph node metastasis excised from the same patient. Although the sample number is small, the chance of obtaining the same p53 mutation independently in both the primary and metastatic tumour of each patient is at least 10(-4), therefore the results indicate that keratinocytes harbouring these p53 mutations possess a selective advantage throughout SCC progression.

Carcinoma, Squamous Cell↗
PubMed1994

Epidermal growth factor receptor expression by human squamous cell carcinomas of the head and neck, cell lines and xenografts.

Epidermal growth factor receptor (EGFR) overexpression has been associated frequently with squamous cell carcinomas (SCC) and SCC cell lines. In most cases the level of EGFR on the tumours from which the cell lines were derived has not been determined, nor have EGFR levels been determined for xenograft tumours from the cell lines. In this study we determined EGFR expression on a new series of head and neck SCC (SCCHN)-derived cell lines, which were obtained from tumours representing a spectrum of malignant progression, and two cell strains derived from erythroplakia premalignant lesions. The level of EGFR on cell lines was determined by [125I]EGF competitive binding assays. EGFR levels on some of the original tumours and xenografts of the cell lines were determined on cryosections by a competitive binding assay based on [125I]EGFR1, an EGFR-specific monoclonal antibody. EGFR expression on the tumour cryosections was compared with expression on cryosections of skin and buccal mucosa. Eight of the ten tumour cell lines had elevated EGFR. Two of the tumour-derived cell lines and the two erythroplakia-derived cell strains expressed EGFR at levels similar to that detected on normal keratinocytes in tissue culture. Only two of the tumours overexpressed EGFR when compared with normal tissue. The other tumours had levels similar to that detected on the basal layers of skin or buccal mucosa. The xenografts expressed EGFR, as did the original tumours, even though they were derived from cell lines that displayed significant overexpression of EGFR. This study suggests that most tumours have a latent potential to overexpress EGFR which is realised in tissue culture.

Animals↗
PubMed1994

The p53 status of cultured human premalignant oral keratinocytes.

Around 60% of oral squamous cell carcinomas (SCCs) have been shown to harbour p53 mutations, and other studies have demonstrated mutant p53 genes in normal and dysplastic squamous epithelium adjacent to these SCCs. In line with these earlier studies we show here that DOK, a keratinocyte cell line derived from a dysplasia, displays elevated levels of p53 protein and harbours a 12 bp in-frame deletion of the p53 gene spanning codons 188-191. In contrast, the coding region of the p53 gene was normal in a series of six benign recurrent laryngeal papillomas and a series of four premalignant oral erythroplakia biopsies and their cell cultures. All but one of these lesions were free of malignancy at the time of biopsy, in contrast to the premalignant lesions studied by previous investigators, but keratinocytes cultured from these lesions all displayed a partially transformed phenotype that was less pronounced than that of DOK. Since three out of four of the erythroplakia patients developed SCC within 1 year of biopsy, these lesions were by definition premalignant. The availability of strains of partially transformed keratinocytes from premalignant erythroplakias which possess normal p53 genes should enable us to test the role of mutant p53 in the progression of erythroplakia to SCC. The premalignant tissues and cultures were also tested for the presence of human papillomavirus (HPV), which is known to inactivate p53 function in some cases. Only the benign papillomas were shown to contain high levels of either HPV 6 or HPV 11 E6 DNA, but not both, and none of the samples contained detectable levels of HPV 16, HPV 18 or HPV 33 E6 DNA or L1 DNA of several other HPV types. There was therefore no evidence to suggest that p53 was being inactivated by a highly oncogenic HPV in these samples.

Biopsy↗
PubMed1994

The influence of the New Pathway curriculum on Harvard medical students.

BACKGROUND: This study evaluated the effect of a radically redesigned curriculum at Harvard Medical School on preclinical students' knowledge, skills, personal characteristics, approaches to learning, and educational experiences. METHOD: Multiple measures were used to collect data from 121 students from the entering classes of 1989 and 1990 who had been randomly assigned to the New Pathway or traditional curricula; all had applied to be in the new curriculum. RESULTS: The New Pathway students reported that they learned in a more reflective manner and memorized less than their control counterparts in the traditional curriculum during the preclinical years. The New Pathway group preferred active learning and demonstrated greater psychosocial knowledge, better relational skills, and more humanistic attitudes. They felt more challenged, had closer relationships with faculty, and were somewhat more anxious than those in the traditional program. There was no difference in problem-solving skills or biomedical knowledge base. CONCLUSION: Students in the new curriculum learned differently, acquired distinctive knowledge, skills, and attitudes, and underwent a more satisfying and challenging preclinical medical school experience without loss of biomedical competence. These findings should encourage other schools to consider such a curriculum.

Clinical Competence↗
PubMed1994

Less acidic forms of luteinizing hormone are associated with lower testosterone secretion in men on haemodialysis treatment.

OBJECTIVE: Men with chronic renal failure treated by haemodialysis have raised levels of bioactive LH (B-LH) and immunoreactive LH (I-LH) but reduced B-LH:I-LH (B:I) ratio and testosterone (T) secretion. This study investigated the LH isoform distribution in serum from normal adult males and males on regular haemodialysis treatment. DESIGN: Four blood samples (2 ml) were obtained at 15-minute intervals from a group of men on regular haemodialysis treatment. These samples were part of a larger pulse profile series and showed no evidence of LH pulsatility. The serum was pooled for each individual patient. Blood (10 ml) was also drawn randomly from healthy male volunteers. The sera were chromatofocused on a 4-ml mono-P column attached to a fast performance liquid chromatography system. This procedure separates the LH isoforms according to their isoelectric point. The pH gradient was between pH 7 and pH 4. PATIENTS: The five men with chronic renal failure were aged between 18 and 40 years and had been on haemodialysis for a mean of 10 months (5-20). They were sampled the night prior to a dialysis session. The five normal healthy volunteers had never had any endocrine disorder diagnosed. MEASUREMENTS: An immunoradiometric assay and a commercially available (Delfia) immunofluorimetric assay were employed for detection of LH in the sera and in chromatofocusing fractions. B-LH and testosterone were also measured in the sera. RESULTS: Hormone data (mean +/- SEM for normal and renal subjects respectively) were 15.5 IU/l +/- 1.2 and 26.9 +/- 7.2 (B-LH), 6.0 IU/l +/- 0.3 and 16.5 +/- 4.8 (irmaLH), 5.7 +/- 0.5 and 13.6 +/- 4.8 (fluorLH), 25.2nmol/l +/- 2.0 and 12.1 +/- 1.2 (T). The serum B:I ratios were 2.6 +/- 0.1 and 2.6 +/- 0.2 (controls, irmaLH and fluorLH respectively) and 1.7 +/- 0.1 and 2.1 +/- 0.1 (chronic renal failure group). Recovery of LH from the column was 111 +/- 12% (mean +/- SEM) by IRMA and 104 +/- 7% by IFMA for the ten FPLC runs. The median pI for the LH distribution measured by both assays was in the region 6.54-6.40 for subjects with chronic renal failure and 6.09-5.95 for controls. Median pI was negatively correlated to the B-LH:irmaLH (P < 0.0001) and B-LH:fluorLH ratios (P = 0.002) in the serum. Furthermore, the proportion of isoforms recovered in the pH region 6.25-5.50 increased with increasing T levels in the serum (P < 0.004). CONCLUSION: The distribution of LH in serum of men on haemodialysis is more basic than in normal men. The greater the proportion of more acidic LH species, particularly those with a pI of between 5.50-6.25, the higher the ratio of LH bioactivity to immunoactivity and consequently testosterone levels.

Adolescent↗
PubMed1994

Monoclonal antibodies to high-incidence Kell epitopes: characterization and application in automated screening of donor samples.

Monoclonal antibodies, LM313/706 and LM357/828, recognize high-frequency epitopes which are absent on red cells of Ko phenotype. Both antibodies have proved suitable for automated screening of blood donor samples, with 5 ml of each culture supernatant sufficient to screen 3,000 donor samples. In a screen of 45,545 samples, LM313/706 revealed 11 samples (1:3686) of Kp(a+b-) phenotype. Thirty-seven samples of K+k- phenotype were identified in 15,235 samples screened with LM357/828 antibody (0.24%). The epitope recognized by LM313/706 was inactivated by 2 mM DTT suggesting a possible association with the Jsa/Jsb antigen structure. The expression of the k-like epitope detected by LM357/828 antibody was found to be influenced by pH change.

Antibodies, Monoclonal↗
PubMed1994

The average daily energy expenditure of elderly males and females.

The aim of this study was to report on the average daily energy expenditure by elderly males and females in their normal day-to-day activities. The study was based on an analysis of data collected over six months from daily diary recording of activities. The subjects, 82 males and 93 females, were non-institutionalized volunteers with a mean age of 68 years. A multivariate analysis of variance indicated that there were no differences between males and females in total mean daily energy expended on Sporting activities. Females expended twice as much energy as males on Household Chores (F = 36.3,p < 0.001). Males expended over three times as much energy as females on gardening (F = 56.7, p < 0.001) and over seven times as much on Maintenance (F = 53.6, p < 0.001). There were also differences between males and females on energy expended while Walking (F = 6.1, p < 0.02) and on Miscellaneous activities (F = 6.3, p<0.05). It is concluded that sex stereotypical roles for activities required at younger ages are continued into old age. The implications of these findings for prescribing regular exercise in the elderly are discussed, indicating specific activities that might prove to be beneficial.

Aged↗