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Biomedical subjects

M L Johnson

Publications and source records attributed to M L Johnson.

At least 253 records · Page 14Linked to original sources

Amino-acid sequence of the alpha and beta chains of adult hemoglobin of the harbor seal, Phoca vitulina.

The complete amino-acid sequences of the alpha and beta chains of adult hemoglobin of harbor seal, Phoca vitulina that belong to carnivora were determined as follows. The alpha and beta chains isolated by chromatography on a CM-cellulose column were digested with trypsin after S-carboxymethylation. Amino-acid sequences of the tryptic peptides derived from both chains were analysed. Comparing the primary structures of the alpha and beta chains of the seal hemoglobin with those of human, dog, bear, badger and cat, 19, 12, 12, 11, and 16 substitutions, respectively, were recognized in the alpha chain, and 12, 10, 4, 6, and 19 (22) in the beta chain.

Amino Acid Sequence↗

A cohort mortality study of painters and allied tradesmen.

A cohort study was conducted of the membership of a large international union of painters and allied tradesmen. The union membership consisted of both painters and associated trades such as glaziers and tile and carpet layers. The study examined the mortality experience of 57 175 current and former union members in four states (California, Missouri, New York, and Texas) in the United States (US) from 1975 through 1979. No excess mortality was observed for the total union membership when compared to that of all US white males. When the study population was subdivided by the trade affiliation, members of locals comprised primarily of painters exhibited a significant elevation in mortality from all malignant neoplasms, lung cancer, and stomach cancer, compared to all US white males. To reduce the impact of potential nonoccupational differences between the study population and all US white males, the data were also analyzed using the entire cohort as the standardization population. Significant elevations continued to be observed for all malignant neoplasms and lung cancer among the membership of painting locals compared to other locals. In addition there was a statistically significant difference in mortality from leukemia and cancer of the bladder observed between the groups.

Adult↗

Aging of the United States population. The dermatologic implications.

Clearly in the near and later future the older patient will augment significantly the burden of dermatologic disease and the consequent need for care. Increasing in numerical strength, those 65 years and older, carrying along the common problems prevalent in every adult age group, will, by living longer, have new problems related to wear, tear, and actinic exposure as well as pharmacologically induced problems arising from needed therapy for other conditions. The predictable challenge to our specialty is formidable.

Aged↗

The analysis of ligand-binding data with experimental uncertainties in the independent variables.

The method of experimental data analysis known as least-squares requires several inherent assumptions to be met in order for the analysis to be statistically correct. In particular, it must be assumed that the experimental uncertainties exist only on the dependent variables. Least-squares is often used for applications where this assumption is not satisfied. An alternative method of data analysis circumvents the assumption that no experimental uncertainty exists in the independent variables. This method, known as maximum likelihood, will produce statistically correct results in cases where experimental uncertainty exists on both the dependent and independent variables. The method can easily be generalized to include cases where the dependent and independent variables are cross-correlated. The method can also be generalized to include non-Gaussian distributions of experimental uncertainties. The examples presented are simulated applications to ligand-binding problems. The general method is, however, applicable to a wide range of problems in biochemistry.

Binding Sites↗

Organization of ganglioside GM1 in phosphatidylcholine bilayers.

Molecules of the ganglioside GM1 are randomly distributed in liquid-crystalline 1-palmitoyl-2-oleoyl phosphatidylcholine bilayers. This conclusion is based on a freeze-etch electron microscopic study using ferritin-conjugated cholera toxin and cholera toxin alone as ganglioside labels. The average number of GM1 molecules under a label is calculated by a novel method from the dependence of the fraction of bilayer area covered by the label on the mole fraction of GM1 in the bilayer.

Animals↗

Prevalence of dermatologic disease in the United States: a review of the National Health and Nutrition Examination Survey, 1971-1974.

The National Health and Nutrition Examination Survey, 1971-1974, provides the only data on the prevalence of dermatologic disease in the United States. Details are given about specific diagnoses, disability, disfigurement, discomfort, and the relationship of skin change to environmental and occupational exposure. One-third of the individuals, which extrapolates to 60 million Americans, had dermatological problems that should have been seen at least once by a physician. Of those, at least a third considered their skin problems to be a handicap, 10% a handicap to employment or housework. These data provide a basis for evaluating the effect of environment and occupation and should be of interest to those concerned with chronic effects of mechanical injury to the skin.

Adolescent↗

Maintenance of milk protein gene expression in a subpopulation of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinoma cells grown on attached collagen gels.

Milk protein gene expression was studied in cell subpopulations of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinoma cells enriched or depleted for casein production grown on attached collagen gels. Culture of these cells in the presence of 10% fetal bovine serum, insulin (5 micrograms/ml), hydrocortisone (10 micrograms/ml), and prolactin (5 micrograms/ml) maintained alpha-, beta-, and gamma-casein and whey acidic protein mRNAs at levels identical to cells isolated from perphenazine-treated rats. Whey acidic protein mRNA levels in the tumor cells relative to the 14-d lactating gland were greater than those of the casein mRNAs. Withdrawal of prolactin from the casein-producing cells resulted in the loss of all four milk protein mRNAs. Subsequent addition of prolactin to the withdrawn cells caused a rapid accumulation of these mRNAs to prewithdrawal levels. Milk protein gene expression in this tumor cell subpopulation is modulated by prolactin (in the presence of insulin and hydrocortisone) in a similar manner to that observed in the normal mammary gland when these tumor cells are cultured on attached collagen gels.

9,10-Dimethyl-1,2-benzanthracene↗

Successful control of lymphangioma circumscriptum by superficial X-rays.

Lymphangioma circumscriptum (LC) is usually treated by excision. Radiotherapy is not considered suitable primary treatment (Kinmonth, 1972). We report a case which was treated by superficial X-rays with almost complete regression. Regression was very slow. Reviewing the literature we discovered that X-ray therapy has never been properly tested for treating this condition. We conclude that this modality of treatment is rational, effective and warrants further testing.

Child↗

Minimizing false-positive errors in hormonal pulse detection.

To explore the problem of type I (false-positive) statistical errors associated with enumerating endocrine pulses, we used the analysis of immunoactive luteinizing hormone (LH) pulses as a paradigm. In this system, the distribution of measurement error was found to approximate a Gaussian pattern. Moreover, the choice of a fixed threshold criterion to identify a hormone pulse (as generally undertaken to date) was shown to yield significantly different false-positive error rates under different experimental conditions. Therefore, we developed a technique to minimize the detection of false-positive signals and to maintain an essentially uniform error rate among different experimental groups. This simple technique requires that the pulse-detection threshold be adjusted in relation to the degree of intra-assay measurement error present. Our method should facilitate the valid comparison of endocrine pulse frequencies in normal physiological states vs. those associated with hormonal deficiency when measurement error is typically greater. In addition, this approach will aid in a more meaningful assessment of pulse concordance between two or more different hormonal species (i.e., in different assays) and will assist in comparisons of pulse properties quantitated in different laboratories. In summary, rates of false-positive pulse detection using conventional fixed-threshold criteria are materially influenced by even small differences in within-assay variance. We present a technique to minimize this type I statistical error and to maintain an essentially uniform error rate among different experimental groups.

False Positive Reactions↗

A quantitative model for the cooperative mechanism of human hemoglobin.

A quantitative model has been developed for the cooperative oxygenation of human hemoglobin. The model correlates the structural and energetic features of ligand-linked subunit interactions within the tetrameric molecule and the coupling of these interactions to the binding of oxygen and Bohr protons. Recent findings are incorporated regarding (i) the sites of regulatory energy change within the tetrameric molecule, (ii) the nature of the Bohr effect for tetramers and dimers, (iii) the fractional Bohr proton release at each stage of oxygenation, (iv) relative probabilities of binding to the alpha and beta chains within the tetramer, and (v) an extensive data base recently obtained on the linked processes of oxygenation, proton binding, and subunit interactions [Chu, A. H., Turner, B. W. & Ackers, G. K. (1984) Biochemistry 23, 604-617]. Least squares minimization was used to evaluate from these data the free energies for the various processes. A special feature of the model lies in the synchronization of Bohr proton release with changes in quaternary structure. This leads to the striking prediction that a major fraction (as much as 30%) of tetramers are in the oxy quaternary structure after the first oxygen is bound. The model provides a rationale for the essential features of regulatory energy control, and it defines several kinds of additional information that are needed for a more complete understanding of the hemoglobin mechanism.

Hemoglobins↗

Single photon emission computed tomograms of the liver: normal vascular intrahepatic structures.

Because of the high target-to-background contrast obtained with single photon emission computed tomography (SPECT), normal intrahepatic vessels approximately 2 cm in diameter may appear as distinct focal defects in tomographic sections throughout the liver even though normal vessels rarely cause such defects on planar images. To assess this problem, five subjects without evidence of liver disease underwent tomography of the liver with Tc-99m sulfur colloid (TSC) and on a separate occasion tomography of the intrahepatic blood pool with Tc-99m autologous red blood cells (RBC). In each case, well demarcated defects were obvious in contiguous TSC liver tomograms in various planes. Direct comparison with RBC tomograms showed that all of these defects corresponded to intrahepatic veins, typically the right portal vein, its posterior branch, and the left portal vein. Knowledge of the intrahepatic vascular anatomy in a variety of tomographic planes, with examination of each defect in multiple orthogonal planes is necessary to avoid false positive interpretations. In some instances a study with RBC may also be required for more conclusive evaluation of defects seen on TSC liver tomograms.

Diagnostic Errors↗

Performance of LH pulse-detection algorithms at rapid rates of venous sampling in humans.

To assess the influence of the sampling rate on the quantitative characterization of pulsatile luteinizing hormone (LH) release, we withdrew blood at 4-min intervals for 8 h in five men and at 1-min intervals for 2 h in six other men. For comparative purposes, significant LH pulses were enumerated by three independent, computerized pulse-detection algorithms currently available. Our results indicate that, although the absolute number of LH pulses detected was influenced by the particular algorithm used and the estimate of intra-assay variance, all three analyses yielded increased pulse-frequency estimates at more intensive rates of venous sampling. Moreover, using a fourth, modified pulse-detection algorithm intended to maximize recognition of true-positive LH pulses while minimizing both false-positive and false-negative pulses, we observed that venous sampling at 4- and 1-min intervals exposed 4- and 12-fold more LH pulses, respectively, than could be discerned at conventional sampling rates. At rapid rates of venous sampling, the pattern of LH pulses comprised high-frequency, low-amplitude LH pulsations superimposed on lower-frequency LH peaks. This pattern suggests that the pituitary gland is responsive to high rates of intermittent neural stimulation. Moreover, these observed profiles are consistent with rapid initial rates of LH disappearance and/or distribution that we could demonstrate after intravenous bolus injections of purified LH in hypogonadotropic volunteers. In conclusion, we have compared results from three different pulse-detection algorithms at various rates of venous sampling and demonstrated a critical influence of sampling rate on apparent LH pulse frequency in humans.

Adult↗

Estimation of ultrasonic attenuation and mean backscatterer size via digital signal processing.

The backscattered rf signals from the lungs of fetal sheep during their last trimester of development were digitized and processed in an attempt to correlate ultrasonic parameters with measured functional parameters related to lung maturation. The broadband, post- TGC , rf signal of a commercial B-mode ultrasonic scanner was digitized at a sampling rate of 25 MHz. Sorting excluded data from regions of rib shadowing and other nonlung structures from analysis. The sorted data were used to estimate the slope of the ultrasonic attenuation coefficient with respect to frequency via linear regression on the average difference of the logarithm of power spectra from separated data segments. The power spectra were also corrected for attenuation, averaged and used to compute the power cepstrum of the backscattered signal which can be related to mean backscatterer radius. Results are presented for eight fetal sheep.

Animals↗