Adsorption of atomic hydrogen on Si(100)-2 x 1 at 400 K.
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Biomedical subjects
Publications and source records attributed to K Griffiths.
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Transforming growth factor alpha (TGF alpha) expression was analyzed immunocytochemically on formalin-fixed wax-embedded sections obtained from 24 benign prostatic hyperplasia (BPH) specimens and 76 prostatic carcinoma tissues, 3 human prostatic tumor xenografts, normal kidney, and salivary gland. Low amounts of TGF alpha immunopositivity were encountered in the epithelium of BPH glandular tissues, whereas in the prostatic adenocarcinoma samples, a greater heterogeneity and intensity of TGF alpha immunostaining was observed. The most intense staining was exhibited by the least differentiated tumors, although a few of these were weakly stained. Statistical analysis of the relationship of histopathological grade of tumor with TGF alpha expression in the carcinomas showed a significant correlation of these parameters, 0.01 > P > 0.001. The expression of the proliferation markers Ki-67 and PCNA was also analyzed in the carcinoma specimens, and the relationship of these to TGF alpha expression indicated that there was no significant correlation in this series of tumors between increased growth activity and TGF alpha expression (p approximately 0.25 with both markers). The prostatic carcinoma xenografts TEN12 and TEN15 contained low levels of immunoreactive TGF alpha, which was uniformly distributed, whilst heterogeneous immunostaining was observed in the uroepithelial xenograft TEN16. In the normal human kidney, TGF alpha was concentrated in the epithelium of the distal convoluted tubules (DCT) and the collecting tubules (CT), and lower amounts were identified in the proximal convoluted tubules (PCT). As in the prostatic carcinomas, the immunostaining was eliminated by prior absorption of the antibody with pure TGF alpha and not with human or mouse EGF. No crossreactivity of the TGF alpha antibody with salivary EGF was demonstrated. This study concludes that, in prostate carcinoma, the least differentiated tumors more often expressed greater amounts immunoreactive TGF alpha; however, no relationship between TGF alpha expression and cellular proliferation markers was found.
A comparison was made between trajectories of reaches to visual targets by 6-months-old infants, with and without lateral prismatic displacement. In the No Prism condition, the major element of the movement veered towards the target, confirming the results of Mathew and Cook (1990). In the Prism condition, the prism did not affect hand position or movement direction at the beginning of the major element, but a lateral displacement was evident by the end of the element. This is taken as evidence that shifts in trajectory during the element were not due to visual guidance. It is suggested instead that these shifts may reflect correction based upon somatic feedback about position in relation to the visually specified goal of the movement. Evidence that the hand approached the virtual target supports the suggestion that any visual guidance was confined to the approach phase of the reach. Nevertheless, it appears that visual guidance was operating at this stage, since movement direction was displaced away from the virtual target and towards the real target.
Wearing a special thermometric brassiere, twenty-five normal women self-measured their breast surface temperature. The subjects averaged 39 years of age and all were parous. Observations were made for one hour each evening for one menstrual cycle under semi-standardized domestic conditions. They also collected daily samples of saliva for radioimmunoassay of progesterone concentration. The surface temperature of the breast is relatively cold around mid-cycle; thereafter, and without interruption in averaged data, the temperature increases steadily by about 1 degree C over the 12 days of the luteal phase; around the time of the menses, it falls rapidly. This heat rhythm does not occur in peri-menopausal low progesterone menstrual cycles or in patients where the breast tissue has been irradiated for cancer treatment.
BACKGROUND: Although patients from some families with the atypical mole syndrome (AMS) are predisposed to melanoma, it is not known how frequently this underlies the apparently sporadic presentation of melanoma. OBJECTIVE: This study was designed to estimate the frequency of the AMS (dysplastic nevus or FAMMM syndrome) phenotype in a population-based study of patients with melanoma in the United Kingdom and to determine the prevalence of the phenotype in the relatives of the patients with AMS. METHODS: The nevi of patients with melanoma and controls in a case-control study, and the nevi of some relatives of patients with AMS, were examined. An AMS scoring system was used to define the AMS phenotype. The familiarity of the AMS phenotype was then determined by screening first-degree relatives of persons with the AMS phenotype. RESULTS: Forty of 266 (15%) of patients with melanoma had the AMS phenotype compared with 7 of 305 (2%) of the controls (odds ratio 7.5, 95% confidence interval 3.4-16.8). Screening of relatives of patients with melanoma who had the AMS phenotype identified the same phenotype within the families, providing evidence that the AMS phenotype in patients with melanoma is predictive of the same phenotype in relatives, consistent with so-called type D1 AMS. CONCLUSION: The AMS phenotype is a potent risk factor for cutaneous melanoma and is present in 15% of patients. Melanoma in the United Kingdom is more common in women than in men, but the AMS phenotype was more frequent in men in this study. It is our hypothesis that the effects of the putative AMS gene are diluted by environmental factors in U.K. women. Screening of relatives of patients with melanoma who have the AMS phenotype may identify persons at increased risk of melanoma.
This paper indicates the potential of saliva as a medium for chronobiological studies. It has principally focussed on the work of the Tenovus Institute for Cancer Research, at the University of Wales College of Medicine over the past decade or more, particularly for steroid hormones, so as to give an authoritative viewpoint based on practical experience. The article discusses issues ranging from technical to clinical aspects of hormone assay in saliva, showing disadvantages and limitations of use. Increasingly, many other investigators are developing and applying assays for salivary steroids and it is timely that such assays become tools in the hands of the chronobiologist. The clinical-biochemical importance of saliva resides also in the fact that in its context it is possible to assay enzymes, toxic substances and drugs.
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Proliferating cell nuclear antigen (PCNA) expression was determined immunohistochemically, using a monoclonal antibody PC10, in 102 prostatic carcinoma samples and in prostate tissue from 21 patients with benign prostatic hyperplasis (BPH). The percentage of cells with stained nuclei ranged from 1% to 58% in the carcinoma specimens and 0% to 10% in the BPH specimens. A semiquantitative scoring system was devised for the degree of PCNA positivity observed in the tumors. Statistical analysis of the PCNA score in relation to the histological grade of the tumors gave a significant positive or negative correlation between these parameters P less than 0.001. No significant correlation between PCNA score was, however, seen with metastatic status, T category (TMN classification) of the primary tumor, or the patient's age at diagnosis. In 65 prostatic cancer patients of known survival, those individuals whose tumors had a PCNA score of +/- (less than 10% of nuclei stained) were compared with those patients whose tumors were either 1+, 2+, or 3+ (greater than 10% of nuclei stained). Life table analysis of the two groups indicated that the patients with the lower PCNA score survived significantly longer than those with the higher PCNA scores, P less than 0.04. Comparison of the Ki-67 expression in frozen sections with the PCNA expression in wax-embedded tissue of 86 prostatic carcinomas was also undertaken. A significant correlation between these two parameters was found, P less than 0.001, although the growth fraction estimated by Ki-67 expression was generally lower than that given by the PCNA scoring system.
Estimation of the growth fraction of 153 prostatic carcinoma specimens employing Ki-67 immunostaining was undertaken and its relationship to various clinical parameters investigated. In prostate specimens, the percentage of tumour nuclei expressing Ki-67 antigen was measured and assigned a Ki-67 score. It was observed that high Ki-67 scores were associated with the poorly differentiated tumours, the correlation of this proliferation marker with histological grade was found to be significant (P less than 0.001). No relationship was observed between the Ki-67 score of the primary tumour with either the patient's age or with the primary tumor stage (T category). The metastatic status of the patient at diagnosis and the Ki-67 score of the tumour were correlated (P less than 0.05), higher Ki-67 scores being associated with M1 disease. Life-table analysis of 86 patients who subsequently received androgen withdrawal therapy, was undertaken with reference to the various Ki-67 scores of their primary tumors. A statistically significant difference in survival times was observed in patients whose Ki-67 values were less than 1% (P less than 0.0001) when compared to those patients whose tumours expressed 1% and over Ki-67 positivity, the former having longer survival times. When patients were subdivided according to their metastatic status and similar life-table analyses were carried out, no statistical difference was found between survival times and Ki-67 scores in M0 staged patients. In the M1 population of patients, however, those patients whose tumours were negative for Ki-67 expression had significantly longer survival times than those patients whose tumours exhibited positive Ki-67 staining (P less than 0.01). Comparing M1 staged patients whose prostate tumor cells exhibited less than 1% Ki-67 positive nuclei with M1 staged patients whose prostate tumour cells contained 1% and higher Ki-67 stained nuclei, a significantly longer survival time was found in the former group of patients (P approximately 0.0001).
Menstrual-cycle profiles of salivary progesterone concentration, obtained by radioimmunoassay of daily samples collected throughout the cycle, were obtained from Thai (n = 232) and British (n = 130) adolescent girls up to 4 years postmenarche. These profiles were graded from 1 to 5 ranging, respectively from concentrations at the detection limit of the assay to profiles generally observed for the mature premenopausal woman. Contingency table analysis of the grade frequencies for Thai-British pairs of girls matched for chronological age and age at menarche (n = 2 x 90) demonstrated that British girls had more mature cycles (22/90) than Thais (11/90) (P less than 0.05) particularly in the first 2 years postmenarche (P less than 0.01). For these matched pairs of girls there was no evidence to support the view that girls with an early age of menarche develop their profiles more quickly following menarche than those with a late age of menarche, as previously reported and which was thought to be important in the development of breast cancer. The findings of this study also suggest that adolescent girls in Britain develop their menstrual cycle profiles of salivary progesterone more quickly than their Thai counterparts and this may be of value in formulating hypotheses regarding any role that ovarian progesterone secretion may have on subsequent breast cancer risk.
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We have compared an "in-house" Tenovus Institute prostate-specific antigen (PSA) assay with four different commercial kits (ELSA-PSA, IRMA-Count PSA, PROS-CHECK PSA and TANDEM-R PSA) that are available in the UK. There was only good correlation and linear regression parameters between the in-house assay and one of the kit methods. The difference in values for the same sample ranged from 2 to 100-fold. These discrepancies are due, in part, to the specificity of the polyclonal and monoclonal antibodies used in the procedures and the differing "hook effects" caused by the binding capacity of the antibody pairs in the immunometric assays. Discrepancies will, however, result from the differing potencies of the standards used for the calibration curves. This data highlights the urgency for the introduction of an internationally accepted reference standard for PSA.
Interelationships between steroid and growth factor regulation of cell proliferation has been examined in two androgen sensitive prostatic cell lines, grown in defined medium. The cell lines used were derived from normal (CAPE) and neoplastic (LNCaP) tissues. The growth of both cell lines was elevated by challenge with serum, androgens and epidermal growth factor (EGF) used as single agents. The effects of androgen in CAPE were small, but significant while the profound effects of these agents on the growth of LNCaP were confirmatory of other studies. Androgens upregulated EGF receptor expression in LNCaP measured by both ligand binding capacity and mRNA analysis. This was not observed in the CAPE cells. Addition of serum (whole or charcoal stripped) suppressed the observed androgenic stimulation of EGF receptor expression in LNCaP. This apparent anomaly is discussed in relation to the growth enhancing properties of serum in these cell lines and in the wider context of normal and neoplastic growth control in the prostate.
Reaches made without feedback to positions on an object's surface reflect the spatial form of the surface. In Experiment 1, the reaching pattern varied with the stimulus surface's spatial attributes, consistent with a point-by-point perceptual representation of the surface. In Experiment 2, systematic reaching errors were determined solely by target position regardless of surface structure, implying a highly consistent representation of location. In Experiment 3, illusory slant was imparted to a surface by an aniseikonic lens. Individual variations in directly judged slant were reflected in the reaching pattern, implying organization of local perceptual representation of location and global perception of spatial attributes of the stimulus into a coherent structure.