Posture, Place, and Mood Effects on Ambulatory Blood Pressure

Ambulatory blood pressure was studied as a function of posture, place, and mood in 131 subjects classified according to race, gender, and hypertensive status. The effect of posture was significant and explained a substantial proportion of within-subject variability. After controlling for posture, significant place and mood effects were observed when subjects were sitting but not when they were standing. Home vs. work differences in both systolic and diastolic blood pressure were significantly greater in Whites than in Blacks. Similar differences in systolic blood pressure were greater in mild hypertensive than in normotensive subjects. The results of this study underscore the need to control for effects of posture when interpreting ambulatory blood pressure readings.     

Chromosome mapping of biological pathways by fluorescence-activated cell sorting and cell fusion: Human interferon gamma receptor as a model system

Human chromosome 6 encodes both the interferon gamma receptor as well as the class I major histocompatability complex antigens, HLA-A, -B, and -C. However, the presence of chromosome 6 in somatic cell hybrids is insufficient to confer sensitivity to human interferon gamma (Hu-IFN-) as assayed by class I HLA induction; it is necessary for both human chromosomes 6 and 21 to reside in the hybrid to generate a response to Hu-IFN-. Treatment of such a hamster-human hybrid, Q72-18, with Hu-IFN- induces the class I HLA antigens. Q72-18 cells selected by fluorescence-activated cell sorting for the loss of class I HLA induction also lost human chromosome 21. Fusions of such cells to a hybrid that contains only human chromosome 21 reconstitutes HLA antigen induction by Hu-IFN-. Furthermore, fusions of hybrids containing a translocated human chromosome 6q and the HLA-B7 gene to a line containing only human chromosome 21 or a translocated 21q also reconstitutes HLA-B7 mRNA and antigen induction by Hu-IFN-. Thus the segregation of cells on the basis of a biological effect by fluorescence-activated cell sorting and reconstitution by hybrid fusion provides a strategy by which some biological pathways can be mapped at a chromosomal level.     

Two factors responsible for the development of denervation hypersensitivity

1. Innervated adult skeletal muscle is sensitive to acetylcholine at the end-plate region only. After denervation the entire muscle membrane becomes chemosensitive. The period of greatest increase in sensitivity in rat soleus muscles following section of the sciatic nerve in the thigh is between 48 and 72 hr post-operatively.2. Direct electrical stimulation was found to prevent the onset of the development of denervation hypersensitivity during the first 2-3 days after nerve section. Thereafter, electrical stimulation only reduced the sensitivity of denervated muscles to acetylcholine (ACh).3. The period of greatest increase in sensitivity follows loss of transmission and degeneration of the nerve terminals. Once this degeneration is under way, electrical stimulation is no longer as effective in preventing the development of denervation hypersensitivity.4. Hypersensitivity is also seen in muscles on which a small piece of thread or degenerating nerve has been placed. Hypersensitivity following these procedures declines within a few days, unlike denervation hypersensitivity which persists until innervation is restored.5. The present results suggest that activity alone cannot prevent the development of hypersensitivity in the presence of degenerating nerve fibres, or muscle damage. Activity does however counteract increased sensitivity. It is suggested that two factors interact to produce denervation hypersensitivity; the presence of degenerating nerve tissue and concomitant cellular changes bring about changes in the muscle fibre membrane causing it to become hypersensitive; and the loss of muscle activity, resulting in the persistence of hypersensitivity until innervation is restored.     

An observational study of variation in GPs' out-of-hours emergency referrals.

Out-of-hours organisations are responsible for the care of patients 70% of the time, and their GPs act as gatekeepers to secondary care services. This observational study identifies the variations in GPs' out-of-hours referral rates to secondary care and factors that could explain these variations. One hundred and forty-nine GPs who worked in one UK general practice out-of-hours cooperative which served 19 practices with 167 000 registered patients. Data on patients who accessed the out-of-hours service over 3 years (2001-2004) were examined. Factors thought to be predictors of variation in referral rates were investigated using logistic regression analysis. There was a fivefold difference in referral rates between the lowest and highest referring quartiles of GPs (OR [odds ratio] = 4.56, CI [confidence interval] = 3.86 to 5.38). The sex (female) of the clinician, the time of the consultation (11 pm to 7 am), and the place of the consultation (home visit) accounted for some, but not all, of the increased referral rates. A doctor working out-of-hours disproportionately influences the fate of the patient, the number of hospital admissions, and extra costs to the health service. There is a need for follow-up studies to investigate the factors associated with referral behaviour, and how the variation relates to patient factors and the resources available. These findings could be used when planning the staffing of out-of-hours services to optimise appropriate care and minimise patients' exposure to unnecessary intrusive and expensive hospital care.     

Beta-catenin abnormalities and associated insulin-like growth factor overexpression are important in phyllodes tumours and fibroadenomas of the breast

The aim of this study was to assess the expression of IGF-I and IGF-II in phyllodes tumours and fibroadenomas and to see if there is any correlation between nuclear beta-catenin expression and IGF-I and IGF-II expression in these tumours. In a previous study, it has been shown that Wnt signalling is important in the pathogenesis of phyllodes tumours of the breast. Epithelial Wnt5a overexpression and stromal Wnt2 overexpression were associated with abnormal, nuclear localization of beta-catenin in the stromal cells of these tumours. However, not all tumours with beta-catenin accumulation showed Wnt overexpression. One other possible cause of beta-catenin accumulation is overexpression of insulin-like growth factors (IGFs), as both IGF-I and IGF-II have been shown to stabilize beta-catenin. In this study, 30 fibroadenomas of the breast were assessed for beta-catenin expression using immunohistochemistry and the results were compared with previous data from 119 phyllodes tumours. In situ hybridization was used to assess IGF-I and IGF-II expression in 23 phyllodes tumours and 16 fibroadenomas. Nineteen phyllodes tumours (83%) showed widespread overexpression of IGF-II and 5/23 (22%) showed widespread overexpression of IGF-I. IGF-I expression correlated with nuclear beta-catenin staining in phyllodes tumours. Malignant phyllodes tumours showed no or little IGF-I expression. There was a degree of nuclear beta-catenin expression in the stroma (weak in 33%, moderate in 27%, and strong in 40%) in all fibroadenomas and nuclear beta-catenin staining correlated with IGF-I overexpression. Extensive IGF-II overexpression was also found in the majority of fibroadenomas (12/16). These results support the hypothesis that IGF-I and IGF-II overexpression may be important in the pathogenesis of fibroepithelial neoplasms of the breast and that IGF-I overexpression is likely to be contributing to the nuclear beta-catenin localization observed in the tumours.     

The importance of the motor nerve for the development of chemosensitivity at the neuromuscular junction

Experiments were performed on kittens to study the role of innervation on the development of the pharmacological responses of the neuromuscular junction. The importance of the nerve for the development of the differing properties of fast and slow muscles was also studied.It was confirmed that the different responses to depolarising drugs of the slow soleus and fast flexor hallucis longus muscles are not apparent during the first week of the animal's life.Even when the motor nerves to these muscles were crossed at this time the alien innervation did not affect the subsequent development of the different responses of fast and slow muscles to suxa- and decamethonium. This suggests that the different properties of the postsynaptic membrane are established very early in the animal's life and that they cannot be changed by altering the innervation.The neuromuscular junctions of these young animals are very insensitive to suxa- and decamethonium. When innervation is delayed, during the early postnatal period, the development of the high sensitivity of the neuromuscular junctions to the blocking and depolarising actions of these drugs was retarded. It is therefore concluded that the motor nerve induces the high chemosensitivity of the adult endplate region.     

Predicting Home and Work Blood Pressure Measurements from Resting Baselines and Laboratory Reactivity in Black and White Americans

The relationship between blood pressure in the laboratory (both at rest and in response to laboratory tasks) and ambulatory blood pressure at home and at work was evaluated. One hundred nineteen normotensive and unmedicated mild-moderate hypertensive black and white females and males participated in laboratory blood pressure monitoring at rest and during four challenging tasks (structured interview, video game, bicycle exercise, and cold pressor test) as well as ambulatory blood pressure monitoring while at home and at work. Baseline blood pressure taken while subjects were at rest was the strongest predictor of ambulatory systolic blood pressure (r = .64) and diastolic blood pressure (r = .77) at work. Among reactivity tasks the strongest predictors of ambulatory blood pressure in the total population were the structured interview and the video game (both psychological tasks) followed by the cold pressor test. Racial comparisons, however, determined that the cold pressor test predicted diastolic blood pressure significantly better for blacks (r = .73) than for whites (r = .40), suggesting a possible difference in blood pressure regulation.     

The significance of argyrophilia in human breast carcinomas

Summary The significance of demonstrating argyrophilia in human breast carcinomas is a complex issue, although there is general agreement that true carcinoid tumours of the breast are rare.A predominantly unselected series of breast carcinomas has been investigated for evidence of argyrophilia using the Churukian Schenk method (Churukian and Schenk 1979), alpha lactalbumin and prealbumin, a marker of neuroendocrine cells.Argyrophilia has been detected in 25% of carcinomas, including all of mucinous types. However, only 4 of the 68 tumours had a diffuse cytoplasmic reaction typical of that seen in neuroendocrine cells. The others showed a focal or subluminal/ peripheral reaction. Those argyrophilic carcinomas with demonstrable alpha lactalbumin had this latter pattern of reactivity, although the milk protein was always detected in lesser amounts by comparison. Prealbumin was only found to varying degrees in eight tumours and the majority of these had a diffuse or focal cytoplasmic argyrophilic reaction.It would appear that in only a small number of breast carcinomas, approximately six percent, does the presence of argyrophilia probably represent neuroendocrine differentiation, whilst in others it is related to the secretory nature of the tumour cells.     

Liposome-mediated gene transfer and expression via the skin

A ß-galactosidase gene expression construct was usedto investigate the effectiveness of gene delivery and expressionwhen DNA/liposome complexes were topically applied to mouseskin in vivo. DNA was complexed with a commercial preparationof N-[1-(2,3-dioleoyloxy) propyl]-N, N, N-trimethyl-ammonium-methyl-sulphate(DOTAP) in a ratio of 1:1.6 (w/w). The DNA rapidly penetratedthe skin and was expressed in the epidermis, dermis and hairfollicles. A DNA concentration of 267 µg/ml DNA was foundto be optimal for efficient transfection. Expression was seenas early as 6 h post-application, persisted at high levels 24and 48 h post-treatment, but was markedly reduced by 7 daysafter application. In conclusion, utilising a commercially availableliposome preparation, topically-applied DNA/liposome complexescan be efficiently delivered and expressed in several cell typeswithin the skin. This simple, non-invasive technique may haveimplications for a number of gene therapy applications.