Non-dimensional quantification of the interactions between hypoxia, hypercapnia and exercise on ventilation in humans.

The purpose of this study was to develop a non-dimensional approach towards the description of interaction between the three respiratory stimuli of hypoxia, hypercapnia and exercise and to use this approach to quantify the relative strengths of their interactions. Only a part of the study related to the overall interaction of the three stimuli is presented here. Nine volunteers took part in the study and their ventilatory responses to hypoxia were measured under four different conditions of rest-eucapnia, rest-hypercapnia, exercise-eucapnia and exercise-hypercapnia. Non-dimensional linear functions of hypercapnia (x), hypoxia (y) and exercise (z) were defined such that a value of one would double the resting ventilation. Non-dimensional ventilation v was derived as: v(x,y,z) = 1+ x + y + z + g1xy + g2xz + g3yz + g4xyz, where g1, g2, g3 and g4 provide non-dimensional measures of the strength of stimulus interaction. These interactions were calculated from the parameters obtained by fitting simple respiratory models to the data. The values for g1, g3 and g4 were significantly different from zero (p < 0.05, t-test). An intriguing result of this study is the overall negative interaction of the three stimuli, which may suggest that the linear, stimulus-response models commonly used to describe respiratory data may not be adequate for describing these complex interactions.

Small intestinal cancer in England & Wales and Scotland: time trends in incidence, mortality and survival.

BACKGROUND: Time trends in mortality from small intestinal cancer have not been studied for the 1990s. OBJECTIVE: To examine secular trends in incidence of, mortality from, and survival from, small intestinal cancer in England & Wales and Scotland from 1975 to 2002, considering also histological type (incidence), subsite (incidence) and indices of social deprivation (incidence and survival). METHODS: Data were extracted from the Scottish Cancer Registry database and the General Register Office for Scotland, and from the National Cancer Intelligence Centre at the Office for National Statistics for England & Wales. RESULTS: Incidence rates for small intestinal cancer increased for both England & Wales and Scotland over the study period. They were highest among older individuals and generally greater for males than for females. Despite the increase in incidence rates, mortality rates from small intestinal tumours tended to remain stable over the study period, and the general trend was towards increasing survival. Indices of social deprivation were not obviously related to the incidence of small intestinal cancer and did not influence survival. CONCLUSIONS: Incidence rates for small intestinal cancer for both England & Wales and Scotland increased in the last quarter of the 20th century, but survival rates improved and mortality rates declined.

Pancreatic cancer in England and Wales 1975-2000: patterns and trends in incidence, survival and mortality.

BACKGROUND: Rates and time trends in mortality from pancreatic cancer vary considerably between countries. AIM: To examine trends and patterns in the incidence of, and the survival and mortality from, pancreatic cancer in England and Wales from 1975 to 2000; in particular, whether incidence and survival rates are related to socio-economic deprivation. METHODS: We calculated annual age-specific and overall age-standardized incidence and mortality rates by sex for pancreatic cancer in total, and by subsite. We also estimated survival by sex and age group and by subsite. RESULTS: In males, the age-standardized rate fluctuated in the late 1970s, to peak at 13.0 per 100,000 in 1979, declined steadily by an average of 1.3% per year to around 10.3 per 100,000 in the mid-1990s and then levelled off. For females, the rate peaked at 8.4 per 100,000 in the late 1980s before declining and fluctuating around 7.7 per 100,000 in the late 1990s. Patterns and trends in mortality rates were closely similar to those in incidence, due to the very low survival rates: only 2-3% at 5 years from diagnosis. Survival rates improved only minimally over the period 1971-99. Incidence and mortality rates were slightly higher in both males and females living in the most deprived areas, but survival was not consistently related to socio-economic deprivation. CONCLUSIONS: The incidence of, and mortality from, pancreatic cancer in England and Wales have fallen from peak levels observed in the 1970s and 1980s, and levelled off in the 1990s for both sexes; survival rates remain very low.

Evolutionary kinship therapy: basic principles and treatment implications.

The idiom of kinship is a powerful one that stretches across many levels of social behaviour (van den Berghe, 1979), and Daly, Salmon & Wilson (1997) recently outlined the basic principles of a comprehensive, evolution-based kinship psychology. Their approach merges traditional kinship theory, Hamilton's inclusive fitness model and the broader realm of evolutionary psychology into an exciting and provocative call to arms. They address biological, psychological (viz. fictive kinship) and kin-like levels of analysis, and they argue for a relationship-specific kinship psychology that deals with the particular demands of being a mother, father, mate, offspring or grandparent. Our particular approach to kinship psychology has focused primarily on the distinction between biological kinship and psychological kinship (Bailey, 1988; Bailey & Wood, 1993; Nava & Bailey, 1991), and more recently on the role of kin-like relations in psychotherapy and other social contexts (Bailey, 1997a; Wood, 1997). The kin-like category is especially noteworthy in modern industrialized countries where acquaintanceships and stranger-to-stranger interactions often predominate over biological and psychological kinships (Ahern & Bailey, 1997).

Characterisation of a repressor gene (xre) and a temperature-sensitive allele from the Bacillus subtilis prophage, PBSX.

The defective prophage of Bacillus subtilis 168, PBSX, is a chromosomally based element which encodes a non-infectious phage-like particle with bactericidal activity. PBSX is induced by agents which elicit the SOS response. In a PBSX thermoinducible strain which carries the xhi1479 mutation, PBSX is induced by raising the growth temperature from 37 degrees C to 48 degrees C. A 1.2-kb fragment has been cloned which complements the xhi1479 mutation. The nucleotide sequence of this fragment contains an open reading frame (ORF) which encodes a protein of 113 amino acids (aa). This aa sequence resembles that of other bacteriophage repressors and suggests that the N-terminal region forms a helix-turn-helix motif, typical of the DNA-binding domain of many bacterial regulatory proteins. The ORF is preceded by four 15-bp direct repeats, each of which contains an internal palindromic sequence, and by sequences resembling a SigA-dependent promoter. The nt sequence of an equivalent fragment from the PBSX thermoinducible strain has also been determined. There are three aa differences within the ORF compared to the wild type, one of which lies within the helix-turn-helix segment. This ORF encodes a repressor protein of PBSX.

Characterization of PBSX, a defective prophage of Bacillus subtilis.

PBSX, a defective Bacillus subtilis prophage, maps to the metA-metC region of the chromosome. DNA (33 kilobases) from this region of the chromosome was cloned and analyzed by insertional mutagenesis with the integrating plasmid pWD3. This plasmid had a promoterless alpha-amylase gene (amyL) that provided information on the direction and level of transcription at the site of integration. Transcription under the control of the PBSX repressor proceeded in the direction metA to metC over a distance of at least 18 kilobases. Electrophoretic analysis of proteins produced by different integrant strains upon PBSX induction and by fragments subcloned in Escherichia coli allowed the identification of early and late regions of the prophage. A set of contiguous fragments directing mutagenic integration suggested that the minimum size of an operon that encodes phage structural proteins is 19 kilobases. The adaptation of PBSX transcriptional and replicational functions to a chromosomally based, thermoinducible expression system is discussed.

Superoxide radical production after phorbol ester stimulation in neutrophils of aged donors.

Superoxide anion radical production was studied in purified neutrophils of young and old donors after stimulation with phorbol 12-myristate 13-acetate to determine whether phorbol-stimulated activation of NADPH-oxidase was altered by aging. Superoxide radical production of neutrophils of healthy ambulatory elderly (mean age 73 years) was increased compared to young adult controls. Expressed as nmol superoxide/min/mg protein, however, old cells were no different from young. Neutrophils of the elderly contained nearly 20% more protein/cell than young cells, yet neutrophil diameter and volume were not increased in the old cells. Binding affinity and maximum binding capacity of 3H-phorbol 12,13-dibutyrate were similar in young and old neutrophils. Maximum binding capacity was similar whether expressed on a per cell or per mg protein basis. Although others have suggested that initial plasma membrane events leading to superoxide radical production are diminished in aging cells, these studies show that intracellular phases of the mechanisms leading to superoxide radical production are maintained. Superoxide production rate per cell is increased in older persons, associated with a higher protein content per cell but not larger cell size.