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Biomedical subjects

D Dix

Publications and source records attributed to D Dix.

At least 19 recordsLinked to original sources
PubMed1997

Characterization of the FET4 protein of yeast. Evidence for a direct role in the transport of iron.

The low affinity Fe2+ uptake system of Saccharomyces cerevisiae requires the FET4 gene. In this report, we present evidence that FET4 encodes the Fe2+ transporter protein of this system. Antibodies prepared against FET4 detected two distinct proteins with molecular masses of 63 and 68 kDa. In vitro synthesis of FET4 suggested that the 68-kDa form is the primary translation product, and the 63-kDa form may be generated by proteolytic cleavage of the full-length protein. Consistent with its role as an Fe2+ transporter, FET4 is an integral membrane protein present in the plasma membrane. The level of FET4 closely correlated with uptake activity over a broad range of expression levels and is itself regulated by iron. Furthermore, mutations in FET4 can alter the kinetic properties of the low affinity uptake system, suggesting a direct interaction between FET4 and its Fe2+ substrate. Mutations affecting potential Fe2+ ligands located in the predicted transmembrane domains of FET4 significantly altered the apparent Km and/or Vmax of the low affinity system. These mutations may identify residues involved in Fe2+ binding during transport.

Biological Transport↗
PubMed1996

Intranigral or intrastriatal injections of GDNF: effects on monoamine levels and behavior in rats.

The present studies were designed to determine whether administration of recombinant human glial cell line-derived neurotrophic factor (rhGDNF) into either the substantia nigra or striatum is capable of augmenting dopamine function of the nigrostriatal pathway in normal rats. Single bolus intracranial injections of rhGDNF at either site increased locomotor activity and decreased food and water consumption and body weight in a dose-dependent manner when compared to vehicle-treated animals. These behavioral responses returned to pre-control levels within 3 weeks post rhGDNF administration. Administration of rhGDNF intranigrally increased dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels of the ipsilateral substantia nigra at 2 and 6 weeks post injection but had no augmenting effects on dopamine or its metabolites in the striatum. Administration of rhGDNF intrastriatally increased DOPAC and HVA levels of the ipsilateral striatum, although striatal dopamine levels were unchanged. Ipsilateral nigral dopamine levels were increased after intrastriatal injection of rhGDNF. The effects of intracranial rhGDNF were not specific to the nigrostriatal dopamine system, since nigrostriatal serotonin, 5-hydroxyindoleacetic acid (5-HIAA), epinephrine and norepinephrine transmitter levels were altered depending on administration route for rhGDNF and dose. Taken together, these data demonstrate long-lasting neurochemical and behavioral changes which suggest that rhGDNF can augment function in adult rat dopamine neurons. Therefore, rhGDNF may have therapeutic potential for Parkinson's disease.

Animals↗
PubMed1996

On the role of aging in carcinogenesis.

Correlation coefficients for age-standardized incidence rates between cancers of the stomach, colon, rectum and lung over place (worldwide) and time (in Connecticut) vary from positive to negative values, indicating that these cancers are not caused by common environmental agents. Correlation coefficients for age-incidence patterns (the variation in age-specific rates with age) between these cancers, on the other hand, are all highly positive for both sexes. We conclude that the carcinogenic determinants that vary with age are common to the cancers studied and to both sexes, and distinct from the carcinogenic determinants that vary with place and time. For the cancers studied, incidence rates are negligible until age 30, at which time they increase dramatically and continue to increase at least until age 75. The rate of increase, however, diminishes continuously with advancing age after 30. We suggest that the role of aging in cancer incidence is determined by two components, one responsible for the dramatic rate increase beginning near age 30 and one responsible for the gradual diminution in that rate increase. The former may correspond to the activation of quiescent cells with damaged DNA or to the deactivation of DNA surveillance or repair or to impaired apoptosis, while the latter may correspond to the loss of cell division potential.

Adult↗
PubMed1994

More on torturing data.

Explore the source record for details and available documents.

Data Interpretation, Statistical↗
PubMed1992

Science as cancer prevention for American inner city residents.

Eighty parents and guardians of high-risk elementary school children from Hartford, America's fourth poorest city, participated in a 12-week Saturday programme of science and cancer risk reduction while their children participated in a science programme designed to be interesting and fun. The children learned to enjoy biology as innovative recreation. Their parents and guardians learned to appreciate the health risks associated with passive thinking. Cigarette advertisements and misleading food claims were exposed to scientific scrutiny with the result that parents and guardians came to view scientific thinking as a means to protect their children and themselves from cancer. They also learned to reduce cancer risk through proper nutrition. Attendance was excellent and the majority of parents and guardians completing the programme believed they had learned to identify and avoid cancer risks.

Adult↗
PubMed1989

The role of aging in cancer incidence: an epidemiological study.

Age-specific and age-standardized incidence rates for cancers of the bronchus, stomach, colon, rectum, pancreas, skin, male bladder, and female breast, uterus, and ovary in 1975 were studied in populations throughout the world, and, for bronchus and stomach cancers, over time from 1960 to 1975. The variation in age-specific rates with age was similar for all cancers, as demonstrated by large positive correlation coefficients between age-incidence patterns averaged over all populations. In addition, the age-incidence patterns for bronchus and stomach cancer were similar and essentially invariant over time. The variation in age-standardized rates among the populations was not similar for all cancers, as demonstrated by correlation coefficients that were small in some cases and negative in others. Between bronchus and stomach cancer, age-standardized rates varied in opposite directions from 1960 to 1975. It is obvious, therefore, that the cause for the variation in age-specific rates with age is not related to the cause for the variation in age-standardized rates among populations or over time. The shape of age-incidence patterns for the cancers studied must be determined by a factor that is common to the tissues of tumor origin, and invariant among populations and over time. The intrinsic aging process is the most reasonable candidate for this role.

Adult↗
PubMed1988

Estimating reference ranges in clinical pathology: an objective approach.

Conventional reference ranges evolve from subjective criteria for health and disease. We offer an objective method for distinguishing typical from atypical values by purely statistical criteria. We define typical values as those exhibiting a linear relationship with percentiles on a value versus percentile plot. Identification of percentiles at which deviation from linearity occurs results from calculation of correlation coefficients between values and percentiles over centrally expanding ranges of percentiles. One selects arbitrarily some minimum value for these correlation coefficients, for example, 0.990, as the criterion for deviation from linearity. Values encompassed by these percentiles of deviation constitute an objective reference range. Identification of any correlations between atypical values and symptoms of disease requires clinical follow-up studies.

Adult↗
PubMed1985

On the role of aging in cancer incidence: an interpretation of the prostate cancer anomaly with implications for routine screening.

Cross-sectional age-incidence patterns for the common male and female cancers in Connecticut were normalized to describe the percentage of total incidence that occurred at each age. The pattern for prostate cancer was atypical--less than the 99% confidence limit from the mean at ages less than 60 and greater than the 99% confidence limit from the mean at ages greater than 75. The available international data on latent carcinoma of the prostate, when normalized as above, resembled the mean male and female cancer patterns in Connecticut and suggested that the atypical behavior of clinical prostate cancer was the result of a lag between the incidence of latent carcinoma and promotion to clinical disease. Confirmation of this suggestion, with the potential to distinguish epidemiologically those latent carcinomas that remain asymptomatic from those that progress to malignancy, awaits routine screening for the latent carcinoma.

Aged↗
PubMed1983

On estimating biological variation in diagnostic tests: application to the oral glucose tolerance test.

Biological variation (BV) in diagnostic tests can be conveniently estimated by the equation, BV = magnitude of reference limit - reference median magnitude of - 2(SD)A, where "reference limit" refers to either the 2.5th or 97.5th percentile in the reference population, magnitude of indicates absolute value, and (SD)A is the standard deviation of random analytical variation at the reference median. The value of (SD)A is calculated from the equation, (SD)A = (CV)A (reference median)/100, where (CV)A, the coefficient of variation of random analytical variation, is obtained from routine stable quality control material. The BV was calculated for plasma glucose concentration at the time points in the oral glucose tolerance test in an asymptomatic reference population and found to vary in the order: fasting less than 3 hour less than 1/2 hour less than 1 hour less than 2 hour. We present correlation coefficients between subject age and plasma glucose concentration that suggest that BV at the fasting, 1/2, 1, and 2 hour points might be reduced by subdividing reference populations according to subject age.

Adolescent↗
PubMed1982

Evaluation of extracranial cerebrovascular disease in the hypertensive patient with ocular pneumoplethysmography at 500 mm Hg.

OPG-300 is a reliable noninvasive method of detecting hemodynamically significant stenoses of the internal carotid circulation. An important limitation of the method is that patients with systemic blood pressure greater than 160 mm Hg cannot be studied; in our laboratory this represented 55 percent of the patients referred for testing. The addition of the 500 mm Hg vacuum modification now allows us to reliably test 95 percent of patients referred to our laboratory for evaluation of the extracranial cerebrovascular circulation.

Blood Pressure↗
PubMed1981

The oral glucose tolerance test: a comparison of the time points on the basis of limit values, normal dispersion, and reproducibility.

Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an individual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, and probability of correct interpretation varies in order: fasting plasma glucose concentration greater than 3-h greater than 2-h greater than 0.5-h greater than 1-h plasma glucose concentration.

Adolescent↗