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Biomedical subjects

D L Johnson

Publications and source records attributed to D L Johnson.

At least 217 records · Page 12Linked to original sources

Field studies: industrial exposures.

The databases and models for the prediction of noise-induced permanent threshold shift (NIPTS) from industrial noise exposures are reviewed. Models available in 1973, compared with later models and data, are shown still to be reasonable. The effect of hearing conservation procedures on the acquisition of new data is discussed. Because of the impact of hearing conservation, new research focus is recommended in three areas: sex differences, newly hired individuals exposed for the first time in occupational noise, and the contribution of nonoccupational noise through the use of questionnaires and dosimetry.

Auditory Fatigue↗

Genetic and environmental effects on carcass characteristics of Southdown x Romney lambs: I. Growth rate, sex, and rearing effects.

Carcass data from more than 4,400 Southdown x Romney ewe and wether lambs collected over a 16-yr period were analyzed for the effects of sex, rearing status, and growth rate. Ewe lambs grew more slowly than wethers and had .78 kg less carcass weight at the same age. The carcass weight advantage for wethers was nearly all caused by heavier fat-free weight. Based on fat depths, the fat on ewe lambs was distributed in more anterior and ventral parts of the carcass relative to wether lambs. Lambs reared as twins had 1.73 kg less carcass weight and correspondingly reduced carcass measurements compared with lambs reared as singles. Sex and rearing status interacted for some traits. However, in no case was a significant sex difference reversed in single- and twin-related lambs. Growth rate effects were determined by regressing average change in carcass measurements on average carcass weight gain over a 5-wk period. When carcass weight remained constant over a 5-wk period, fat weight increased by .12 kg, fat-free weight and muscle measurements decreased, and bone lengths increased. For each kilogram of increase in 5-wk carcass weight gain, the marginal increase in fat weight was .41 kg and that of fat-free weight was .59 kg. At the average 5-wk carcass weight gain of 1.4 kg, fat and fat-free gains were As carcass weight gain increased above 1.4 kg, fat-free gain exceeded fat gain.

Adipose Tissue↗

Genetic and environmental effects on carcass characteristics of Southdown x Romney lambs: II. Genetic and phenotypic variation.

Approximately 4,400 crossbred lambs from Southdown sires and Romney ewes were slaughtered at approximately 18, 23, and 28 wk of age over a 16-yr period. Live weights, carcass measurements, and chemical percentages were analyzed to estimate genetic and phenotypic parameters. Heritabilities of postweaning weights and gains were about .20. Heritabilities of fat and water percentages were about .35 adjusted for age. Heritability of kidney fat percentage was .53. Heritabilities of fat depth and muscle measurements ranged from .21 to .37. Crutch depth (h2 = .73) and cannon bone length (h2 = .74) were the most highly heritable carcass measurements. The genetic correlation between carcass fat and fat-free weight was .47 when lambs were slaughtered at a constant age. Fat-free weight was nearly uncorrelated with percentages of fat, water, and protein when lambs were slaughtered at the same age. Carcass measurements increased accuracy of selection for fat-free weight at a constant age very little compared with using only carcass weight. However, this does not mean that additional measurements are useless. The addition of carcass measurements to the selection criteria would result in correlated responses in chemical composition that more closely resembled direct selection for fat-free weight. Carcass weight would be of little value when used by itself to reduce fat weight adjusted for carcass weight. Direct measurement of carcass composition resulted in 1.6 to 2.6 times more predicted response for reduced fat weight than any combination of carcass weight and one fat depth measurement.

Adipose Tissue↗

Sources and control of error in industrial hygiene measurements.

Many sources of error exist in industrial hygiene measurements. Errors may be systematic or random. Eliminating or controlling systematic and random error during measurement, analysis, and data interpretation is a matter of aggressive quality control/quality assurance and appropriate statistical treatment of data. The occupational health care professional should be aware of error sources in industrial hygiene measurements and be on the lookout for flawed exposure estimates.

Bias↗

Direct demonstration of the active salvage of preformed purines by murine tumors.

The purine de novo biosynthetic pathway has become a target for chemotherapeutic agents and because of the possible contribution of the salvage of extracellular purines to cellular purine pools an examination of the ability of mouse tumors in vivo to exploit the salvage pathways was undertaken. Our data reveal that circulating radiolabeled preformed purines are rapidly and actively salvaged in both normal liver and in two different types of model tumors. The salvaged purines were found to be distributed between both acid soluble cytoplasmic purines and acid insoluble nucleic acid associated purine species. The ability to salvage adenine, the most abundant circulating purine in C57BL/6 mice, was highest in normal liver with the two different model tumors demonstrating lower specific activities of salvaged acid soluble purines. The amount of radiolabel incorporated into acid insoluble nucleic acid was dependent upon the tumor type. Because of the active salvage observed in these tumors, the mechanism by which de novo purine biosynthesis inhibitors serve as effective chemotherapeutic agents may be more complex than simple biosynthetic inhibition.

Adenocarcinoma↗

Comparison of two sample collection methods for quantitative bacteriologic culture of canine prostatic fluid.

Ejaculate, urine, urethral swab specimens, and ultrasonography-guided small-needle prostatic cyst aspiration and/or tissue core biopsy specimens were collected for bacteriologic culture from 25 dogs in which prostatic disease was suspected on the basis of history, clinical signs of disease, or results of physical examination. The prostate gland in each dog was examined ultrasonographically, and the tissue core biopsy specimens were examined histologically and bacteriologically. Two methods were used to assess bacterial prostatitis. In 5 dogs (20%), bacteriologic culture results of paired urethral swab and ejaculate specimens differed from culture results of specimens obtained by needle aspiration of prostatic cyst fluid or tissue core biopsy. The prostate gland in 17 dogs had 1 or more cystic, fluid-filled structures (0.5 to 4.0 cm in diameter). Ultrasonographic appearance of the prostate gland did not have obvious correlation with culture results from dogs of the study. Histologic results of prostatic tissue core biopsy specimens correlated well with culture results.

Animals↗

Epizootiologic evaluation and quantitative analysis of urinary calculi from 150 cats.

One hundred fifty specimens of urinary calculi from 150 cats were analyzed by at least 1 of 4 quantitative methods. Struvite (magnesium ammonium phosphate) was the predominant mineral substance encountered, with 104 (69%) of the calculi being composed entirely of struvite and 23 (15%) being composed partially of struvite. Most (93%) of the calculi were located in the urinary bladder. Growth of bacteria was observed in samples from calculi or urine from 30 (41%) of 74 cats. Coagulase-positive staphylococci were isolated from the urine or calculi from 17 cats (45% of bacteria isolated). Ten other bacterial species were isolated. Median and mean ages of the cats were 5.0 and 5.1 years, respectively. Domestic short-hair and domestic longhair breeds predominated. Fifty-seven percent of the calculi came from females, 43% from males. The distribution by gender did not differ significantly (P greater than 0.2) among the 3 groups (domestic shorthair, domestic longhair, and other). However, the distribution of struvite calculi differed significantly (chi 2 = 15.5, P less than 0.001) by age and gender; among cats less than or equal to 2 years of age, males predominated 2:1 over females, and among cats greater than 2 years of age, females predominated by nearly 3:1 over males. When compared with the general population, females greater than 2 years old were significantly (chi 2 = 15.4, P less than 0.001) overrepresented.

Age Factors↗

Subcloning, characterization, and affinity labeling of Escherichia coli glycinamide ribonucleotide transformylase.

Glycinamide ribonucleotide transformylase (GAR TFase; EC 2.1.2.2) has been purified 70-fold to apparent homogeneity from Escherichia coli harboring an expression vector encoding the purN gene product, GAR TFase. The protein is a monomer of Mr 23,241 and catalyzes a single reaction. Steady-state kinetic parameters for the enzyme have been obtained. The structural requirements for cofactor utilization have been investigated and found to parallel those of the multifunctional avian enzyme. The enzyme was inactivated with the affinity label N10-(bromoacetyl)-5,8-dideazafolate in a stoichiometric and active-site-specific manner. The ionization state of the cofactor analogue in the enzyme-cofactor complex appears to require the dissociation of the proton at N3 of the pyrimidine within the complex.

Acyltransferases↗

The diagnosis and treatment of pediatric lumbar spine injuries caused by rear seat lap belts.

Over the past 3 years, during a time when seat belt use has increased, we have managed nine midlumbar spine fractures in children caused by standard rear seat lap belts. Children with a lap belt injury typically complained of abdominal and back pain, and the nature of their injuries was evident by the presence of a belt-shaped abrasion across the lower abdomen. Midlumbar spine fracture may be associated with paraplegia and life-threatening visceral injury. If the spine is analyzed as a beam, the full spectrum of the reported injuries is predictable. This study shows that the rear seat belts installed as standard equipment do not meet the special needs of children. Rear seat lap belts are better than no restraints, but the addition of a shoulder restraint is strongly advocated to reduce lumbar spine injury.

Adolescent↗

Molecular and expression analysis of the negative regulators involved in the transcriptional regulation of acid phosphatase production in Saccharomyces cerevisiae.

The PHO80 and PHO85 gene products encode proteins necessary for the repression of transcription from the major acid phosphatase gene (PHO5) of Saccharomyces cerevisiae. The deduced amino acid sequences of these genes have revealed that PHO85 is likely to encode a protein kinase, whereas no potential function has been revealed for PHO80. We undertook several approaches to aid in the elucidation of the PHO80 function, including deletion analysis, chemical mutagenesis, and expression analysis. DNA deletion analysis revealed that residues from both the carboxy- and amino-terminal regions of the protein, amounting to a total of 21% of the PHO80 protein, were not required for function with respect to repressor activity. Also, 10 independent single-amino-acid changes within PHO80 which resulted in the failure to repress PHO5 transcription were isolated. Nine of the 10 missense mutations resided in two subregions of the PHO80 molecule. In addition, expression analysis of the PHO80 and PHO85 genes suggested that the PHO85 gene product was not necessary for PHO80 expression and that the PHO85 gene was expressed at much higher levels in the cell than was the PHO80 gene. Furthermore, high levels of PHO80 were shown to suppress the effect of a PHO85 deletion at a level close to full repression. Implications for the function of the negative regulators in this system are discussed.

Acid Phosphatase↗

Heart and heart-lung transplantation at the Johns Hopkins Hospital.

Since 1983, 120 patients have undergone heart transplantation and 18 patients have had heart-lung transplants at our institution. Transplantation is limited only by donor referrals but relaxation of donor criteria has increased donor availability. Immunosuppression currently consists of a 3-drug protocol of CsA, Aza, and P. Our current 1- and 5-year survival rates for heart transplants are 85% and 66%, respectively. The 1-year survival for heart-lung transplantation is 53%. Research continues in many areas of transplantation. The development of coronary artery disease in grafted hearts remains a problem. We have found that older donor age and Cmv infection are significant predictors of developing coronary disease. Routine successful extended heart-lung preservation has been difficult to achieve. A successful technique of prolonged preservation would allow for better matching, reduced logistics, and, potentially, increased numbers of donor organs.

Age Factors↗

The lap belt complex: intestinal and lumbar spine injury in children.

The "seatbelt syndrome" describes intestinal and spinal injury caused by lap-style automotive restraints. More than 2,600 children were admitted to Children's National Medical Center with blunt injury in 3 years; 395 were involved in a motor vehicle crash. Ninety-five of the crash occupants (24%) were known to be wearing safety belts. Ten children sustained a "lap belt injury": five with lumbar spine injury, four with combined lumbar spine and intestinal injuries, and one child with intestinal injury. All ten children presented with a characteristic transverse abdominal ecchymosis. The CT scan was unreliable in evaluation of both spinal and intestinal injury. Lateral radiographs were required for definitive diagnosis in eight of nine children with lumbar spinal injury. CT scan was clearly diagnostic in only one of five children with intestinal injury. Children wearing lap belts are at risk of a "lap belt complex." Lateral spine X-rays, peritoneal lavage, and early laparotomy are recommended to establish an accurate diagnosis and to decrease morbidity.

Accidents, Traffic↗

Mutagenesis by single site-specific arylamine-DNA adducts. Induction of mutations at multiple sites.

Two related carcinogen adducts, N-(deoxyguanosin-8-yl)-2-aminofluorene (AF) or N-(deoxyguanosin-8-yl)-N-acetyl-2-aminofluorene (AAF), were introduced into the lacZ' gene at base position 6253 of the minus strand of M13mp9 viral DNA. The construction of this site-specifically modified DNA was accomplished by first preparing a gapped heteroduplex missing 7 nucleotides at position 6251-6257 followed by ligation with an unmodified heptamer or with a heptamer containing either an AF or AAF adduct. These site-specifically modified templates were transfected into competent wild-type Escherichia coli cells (JM103) and a uvrA strain (SMH12). The mutation spectrum was determined by phenotypic selection of colorless plaques indicating a defective beta-galactosidase marker enzyme and by an in situ hybridization procedure to detect single base pair mismatches in the adduct region. DNA sequencing was used to characterize 179 of the mutants obtained. We found that both adducts were capable of inducing base substitution mutations at the adduct site and in the local region of the adduct. A specific frameshift (+1G) was also observed at a displaced site. All of the frameshift mutations occurred at the ligation site of the modified oligonucleotide. Control experiments with an unmodified oligonucleotide did not show an enhancement of mutations at this site, indicating that the adducts may have been responsible for these frameshifts. The mutations spectra induced by these adducts suggest that mutagenesis depends not only on adduct structure but also the sequence in which the adduct is located and the host cell type used for mutation expression.

2-Acetylaminofluorene↗

Interaction of yeast transcription factor IIIC with dimeric Schizosaccharomyces pombe tRNA(Ser)-tRNA(Met) genes.

A unique tRNA(Ser)-tRNA(Met) tandem gene arrangement was characterized previously from Schizosaccharomyces pombe. Three alleles exist in which a tRNA(Ser) gene is separated by 7 base pairs from an initiator tRNA(Met) gene. Promotion of transcription occurs only within the tRNA(Ser) gene, yielding a dimeric precursor transcript. Using nuclease protection and gel retardation assays, we have analyzed how the Saccharomyces cerevisiae RNA polymerase III transcription factor C (TFIIIC) interacts with this dimeric gene template. The primary interaction site of TFIIIC with the tRNA(Ser) gene is at the 3'-internal control region (ICR), which can be distinguished kinetically from its weaker interaction with the 5'-ICR of the gene. We examined a variety of point mutations and double mutations within the tRNA(Ser) gene which reduce transcription. We found that changes in highly conserved nucleotides within the ICRs reduce TFIIIC binding up to 7-fold compared with the parent suppressor gene. The interaction of TFIIIC with the tRNA(Ser) gene does not sterically prevent stable binding of TFIIIC to the 3'-ICR of the tRNA(Met) gene. However, the affinity of binding of TFIIIC to the dimeric template is 7-fold higher than to the tRNA(Met) gene, alone, demonstrating that the tRNA(Met) gene contains intrinsically weak promoter elements. This may contribute to the inability of the tRNA(Met) gene to independently direct transcription from its ICR elements.

Alleles↗

Preliminary crystallographic investigations of glycinamide ribonucleotide transformylase.

Crystals of glycinamide ribonucleotide transformylase have been grown from 0.4 to 1 M ammonium sulfate, 0.6 to 1 M sodium-potassium phosphate, or 0.65 to 1 M citrate in the pH range 4.5-7.0. The single crystals display variable morphology with varying pH. The crystals belong to the orthorhombic space group C222 with cell dimensions a = 141.4 A, b = 98.2 A, c = 103.5 A. Co-crystals have also been obtained in the presence of the inhibitor 5,8-dideazafolate (KI = 18 microM) under similar crystallization conditions. Crystals of a chemically modified enzyme, iodinated at Cys-21, were grown under similar conditions within the pH range 6.5-7.0. These crystals are isomorphous with the unmodified enzyme. Crystals suitable for high resolution (less than 2.5 A) x-ray diffraction studies have been obtained for each of the above.

Acyltransferases↗

Relative contribution of "determinant selection" and "holes in the T-cell repertoire" to T-cell responses.

Using BALB/c and CBA/J mice, the I-region associated (Ia) binding capacity and T-cell immunogenicity of a panel of 14 overlapping peptides that span the entire sequence of the protein staphylococcal nuclease (Nase) was examined to evaluate major histocompatibility gene complex (MHC) control of T-cell responses. Ia binding and Ia-restricted T-cell immunogenicity could be determined for a total of 54 peptide-MHC combinations. Only 30% of the 54 instances examined involved detectable Ia binding, but they represented almost all (12 of 13) of the immune responses found. However, binding to Ia was not sufficient to ensure T-cell immunogenicity, since only 70% of the binding events were productive--i.e., were associated with an immune response. Thus, Ia molecules have the expected characteristics of a highly permissive capacity for antigen interaction that allows them to function as restriction elements for a large universe of antigens. On the other hand, since the Ia molecules cannot distinguish between self and non-self, not all antigen-Ia interactions would be permitted to elicit a T-cell response. It appears that both Ia binding ("determinant selection") and T-cell repertoire act in concert to define the immune response status of an individual toward any particular T-cell epitope.

Animals↗