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Biomedical subjects

J Howard

Publications and source records attributed to J Howard.

At least 199 records · Page 11Linked to original sources

Prenatal exposure to drugs: behavioral distortions reflecting CNS impairment?

In order to disentangle the effects on development of prenatal drug exposure from the effects of poor prenatal care, perinatal complications, and low socioeconomic status, toddlers prenatally exposed to drugs were compared to high risk preterm toddlers of similar ethnicity and social class. Intellectual functioning and quality of play were assessed. The drug exposed toddlers had significantly lower developmental scores and less representational play. Furthermore elements of their play were characterized by the investigators as a soft neurological sign. The question of possible CNS impairment is raised.

Central Nervous System Diseases↗

Recurrent vulvovaginal candidiasis. A gynaecological enigma.

This article draws attention to a common condition that causes women, their partners and, to a lesser extent, their doctors considerable distress. A review of the recent literature gives an idea of the present scientific thinking on the pathogenesis and management of recurrent vulvovaginal candidiasis.

Candidiasis, Vulvovaginal↗

The fragmentation of 670A MeV neon-20 as a function of depth in water. I. Experiment.

We present the final analysis of an experiment to study the interaction of a beam of 670A MeV neon ions incident on a water column set to different thicknesses. The atomic number Z (and, in some cases, the isotopic mass A) of primary beam particles and of the products of nuclear interactions emerging from the water column close to the central axis of the beam was obtained for nuclei between Be (Z = 4) and Ne (Z = 10) using a time-of-flight telescope to measure the velocity and a set of silicon detectors to measure the energy loss of each particle. The fluence of particles of a given charge was obtained and normalized to the incident beam intensity. Corrections were made for accidental coincidences between multiple particles triggering the TOF telescope and for interactions in the detector. The background due to beam particles interacting in beam line elements upstream of the detector was calculated. Sources of experimental artifacts and background in particle identification experiments designed to characterize heavy ion beams for radiobiological research are summarized, and some of the difficulties inherent in this work are discussed. Complete tables of absolutely normalized fluence spectra as a function of LET are included for reference purposes.

Ions↗

Compliance of the hair bundle associated with gating of mechanoelectrical transduction channels in the bullfrog's saccular hair cell.

Mechanical stimuli are thought to open the transduction channels of a hair cell by tensing elastic components, the gating springs, that pull directly on the channels. To test this model, we measured the stiffness of hair bundles during mechanical stimulation. A bundle's compliance increased by about 40% at the position where half of the channels opened. This we attribute to conformational changes of transduction channels as they open and close. The magnitude and displacement dependence of the gating compliance provide quantitative information about the molecular basis of mechanoelectrical transduction: the force required to open each channel, the number of transduction channels per hair cell, the stiffness of a gating spring, and the swing of a channel's gate as it opens.

Animals↗

Effect of gut-derived acetate on glucose turnover in man.

1. The effect of acetate absorbed from the gut on glucose turnover has been determined in four healthy subjects during both fasting and an intravenous glucose infusion by using [U-13C]glucose. 2. In the first part of the study, after an overnight fast, a tracer dose of [U-13C]glucose was infused at a constant rate along with an infusion of saline for 7 h. In the second part the saline infusion was replaced by glucose at 4.25 mg min-1 kg-1. In both studies 15 mmol of sodium acetate was given by mouth at 15 min intervals from the fourth to the sixth hour. Glucose turnover, respiratory quotient, metabolic rate and blood levels of acetate, 3-hydroxybutyrate, lactate, insulin, glucagon and gastric inhibitory polypeptide were measured. 3. Glucose turnover rates (means +/- SEM) were 1.88 +/- 0.1 mg min-1 kg-1 during fasting and 4.0 +/- 0.08 mg min-1 kg-1 during glucose infusion. Acetate had no effect on glucose turnover, insulin, glucagon and gastric inhibitory polypeptide levels, but temporarily halted the rise in free fatty acids seen during the fasting study. No changes in oxygen consumption or carbon dioxide output occurred, in keeping with previous observations that acetate substitutes for lipid oxidation during metabolism and has no direct effect on glucose turnover.

3-Hydroxybutyric Acid↗

Comparison of the image quality of intravenous urograms using low-osmolar contrast media.

Almost equivalent, intravenous iodine doses of the three new low-osmolar contrast media, ioxaglate (Hexabrix), iopamidol (Niopam) and iohexol (Omnipaque) have been compared for image quality on the intravenous urogram. Generally good radiographic images were obtained. Iohexol gave better results for the nephrogram and pelvicalyceal distension compared with the other contrast media, but only the nephrogram results were statistically significant. Pyelographic density and ureteric distension and density were similar with all three contrast media. In patients where low-osmolality contrast media need to be used for intravenous urography, we suggest that iohexol gives the best radiographic images. Other factors, such as cost and the relative incidence of side-effects of the low-osmolar contrast media also need to be taken into consideration.

Humans↗

Microdosimetry near the trajectory of high-energy heavy ions.

Single-event energy distributions were measured in a 1.3-micron-diameter site as a function of radial distance from the trajectory of high-energy iron ions having an energy of about 600 MeV/amu. It was found that beyond distances of a few micrometers the average lineal energy of the (mostly single) secondary electrons (delta rays) is of the order of 3 keV/micron. This is similar to the value found in a medium irradiated by 170-keV photons. The frequency-mean specific energy for delta rays occurring at large distances from the path of the primary ion exceeds the calculated (radial) absorbed dose by two orders of magnitude.

Ions↗

The intracellular pupil mechanism and photoreceptor signal: noise ratios in the fly Lucilia cuprina.

The function of the intracellular pupil mechanism is examined by comparing the responses of photoreceptors in normal flies with those from white-eyed flies that lack the pupil. In white-eyed flies the response to an intensity increment of fixed contrast decreases at high background intensities. There is a smaller decrease in noise amplitude so that the signal:noise ratio falls. The intensity dependence of the photoreceptor signal:noise ratio fits a simple model in which activated photopigment molecules compete for 3 X 10(4) transduction units. The signal:noise ratio decreases at high intensities because the transduction units are saturated. This model is supported by a noise analysis, which provides three estimates of the number of events generating photoreceptor responses. In white-eyed flies the event number saturates at high background intensities, suggesting that a maximum of 2 X 10(4) events can be simultaneously active. Wild-type flies do not exhibit saturation effects over the range of intensities studied. The signal:noise ratio rises with intensity to reach a stable asymptote, close to the maximum observed for white-eyed flies. Pupil attenuation is calculated from measurements of signal:noise ratio in white-eyed and wild-type flies. The pupil is progressively activated over a two log unit intensity range and when fully closed attenuates the effective intensity by 99%. The threshold of this pupil effect coincides with the threshold of pupil activation measured optically. We conclude that the intracellular pupil attenuates the light flux to prevent receptor saturation and to extend the range of intensities at which fly photoreceptors operate close to their maximum signal:noise ratio. This upper limit is determined by the number of transduction units generating a cell's response.

Animals↗

Synaptic limitations to contrast coding in the retina of the blowfly Calliphora.

We investigate the effects of synaptic transmission on early visual processing by examining the passage of signals from photoreceptors to second order neurons (LMCS). We concentrate on the roles played by three properties of synaptic transmission: (1) the shape of the characteristic curve, relating pre- and postsynaptic signal amplitudes, (2) the dynamics of synaptic transmission and (3) the noise introduced during transmission. The characteristic curve is sigmoidal and follows a simple model of synaptic transmission (Appendix) in which transmitter release rises exponentially with presynaptic potential. According to this model a presynaptic depolarization of 1.50-1.86 mV produces an e-fold increase in postsynaptic conductance. The characteristic curve generates a sigmoidal relation between postsynaptic (LMC) response amplitude and stimulus contrast. The shape and slope of the characteristic curve is unaffected by the state of light adaptation. Retinal antagonism adjusts the characteristic curve to keep it centred on the mean level of receptor response generated by the background. Thus the photoreceptor synapses operate in the mid-region of the curve, where the slope or gain is highest and equals approximately 6. The dynamics of transmission of a signal from photoreceptor to second-order neuron approximates to the sum of two processes with exponential time courses. A momentary receptor depolarization generates a postsynaptic hyperpolarization of time constant 0.5-1.0 ms, followed by a slower and weaker depolarization. Light adaptation increases the relative amplitude of the depolarizing process and reduces its time constant from 80 ms to 1.5 ms. The hyperpolarizing process is too rapid to bandlimit receptor signals. The noise introduced during the passage of the signal from receptor to second-order neuron is measured by comparing signal:noise ratios and noise power spectra in the two cell types. Under daylight conditions from 50 to 70% of the total noise power is generated by events associated with the transmission of photoreceptor signals and the generation of LMC responses. According to the exponential model of transmitter release, the effects of synaptic noise are minimized when synaptic gain is maximized. Moreover, both retinal antagonism and the sigmoidal shape of the characteristic curve promote synaptic gain. We conclude that retinal antagonism and nonlinear synaptic amplification act in concert to protect receptor signals from contamination by synaptic noise. This action may explain the widespread occurrence of these processes in early visual processing.

Action Potentials↗

Effects of heavy ions on rabbit tissues: induction of DNA strand breaks in retinal photoreceptor cells by high doses of radiation.

Excised retinas from New Zealand white (NZW) rabbits were irradiated at 0 degrees C with 9-260 Gy (depending on the type of radiation) of 300 kVp X-rays, or the first 5 cm (range: approximately 14 cm in water) of 365 MeV/u Ne ions or 530 MeV/u Ar ions (LET infinity's: approximately 1, 35 +/- 3 and 90 +/- 5 keV/micron, respectively). Other positions (LET infinity's) in the Ne-ion beam (Bragg curve) were employed in more limited experiments. The retinas were frozen and stored in liquid nitrogen until analysis. Total strand breakage in the DNA of retinal photoreceptor (sensory) cells was determined from sedimentation profiles obtained by velocity sedimentation through reoriented alkaline sucrose gradients under conditions free from anomalies related to rotor speed. For the radiation doses employed: the reciprocal of the number average molecular weight, Mn, was related linearly to dose for each radiation quality and extrapolation to zero dose in each case gave positive intercepts for which the mean unirradiated molecular weight, M0, was 6.1 +/- 1.0 X 10(8) daltons; the efficiencies of total strand breakage for the different radiations were 50 +/- 3, 110 +/- 2 and 240 +/- 6 eV/strand break, respectively. For the heavy ions, accurate analogous calculations for other positions in the Bragg curves were precluded by beam degeneration due to fragmentation of the primary particles, etc. Overall, the experimental results support the concept that ionizing radiations damage cellular DNA by two general processes. One process causes localized damage, which under our experimental conditions is revealed as strand breaks and/or alkali-labile bonds in regions between molecules of size circa 10(9) daltons (subunits); the other causes essentially random damage. Base damage caused by either process would not have been delineated in our experiments.

Animals↗

'Avoidable mortality' from cervical cancer: exploring the concept.

The National Cancer Institute of the United States is encouraging research aimed at reducing 'avoidable mortality' from cancer. This article explores the meaning of the concept from a cancer-control perspective. Using cervical cancer as the focus of discussion, the author examines reference standards and social constraints that can help define the boundaries of avoidable mortality. The article considers the implications of voluntary participation in screening programs, the negative association between risk status and screening frequency, errors in collecting and interpreting Pap smears, improper and incomplete followup, and selected intervals for screening tests. To reach underscreened populations who are at high risk of cervical cancer, prevention strategists must create opportunities for intervention through innovative 'outreach' and 'inreach' programs. Inreach strategies exploit opportunities for cancer screening within the existing health-care process. Possibilities for reducing mortality from cervical cancer depend on more than the state of science. The likelihood of change is also a function of social priorities, social commitments, and the allocation of resources to social technologies that can effect change.

Adult↗

Mechanical relaxation of the hair bundle mediates adaptation in mechanoelectrical transduction by the bullfrog's saccular hair cell.

Mechanoelectrical transduction by hair cells of the frog's internal ear displays adaptation: the electrical response to a maintained deflection of the hair bundle declines over a period of tens of milliseconds. We investigated the role of mechanics in adaptation by measuring changes in hair-bundle stiffness following the application of force stimuli. Following step stimulation with a glass fiber, the hair bundle of a saccular hair cell initially had a stiffness of approximately equal to 1 mN X m-1. The stiffness then declined to a steady-state level near 0.6 mN X m-1 with a time course comparable to that of adaptation in the receptor current. The hair bundle may be modeled as the parallel combination of a spring, which represents the rotational stiffness of the stereocilia, and a series spring and dashpot, which respectively, represent the elastic element responsible for channel gating and the apparatus for adaptation.

Acclimatization↗

Factors affecting the level of kanamycin resistance in transformed sunflower cells.

A 230 base pair DNA segment containing the sequences 5' to the 700 to 750 nucleotide (nt) transcript 7' (ORF 3; RF Barker, KB Idler, DV Thompson, JD Kemp 1983 Plant Mol Biol 2: 335-350) of the octopine tumor inducing plasmid pTiA6 has been isolated. This region has (a) 180 base pairs of DNA upstream of the TATA box, (b) the start of RNA synthesis, and (c) the entire 5' untranslated region of the gene. We have fused this presumed promoter fragment to the neomycin phosphotransferase II (NPTII) gene from Tn5 in a plant expression cassette. After recombination into a tumor inducing plasmid delivery plasmid, this cassette confers selectable kanamycin resistance to transformed sunflower cells. Removal of the out-of-frame ATG in the 5' leader sequence of the NPTII gene by two different modifications increased both the levels of NPTII enzyme activity and the ID(50) for kanamycin in the tumor cells. The promoter region of the transcript 7 gene gives levels of kanamycin resistance equivalent to the nopaline synthase promoter and octopine synthase promoter when used in the same constructions and assayed in the same tissues.

Journal Article↗