Search PubMed⌕ Search

Biomedical subjects

S L Johnson

Publications and source records attributed to S L Johnson.

At least 91 records · Page 5Linked to original sources

TSF3, a global regulatory protein that silences transcription of yeast GAL genes, also mediates repression by alpha 2 repressor and is identical to SIN4.

TSF3 encodes one of six (TSF1 to TSF6) recently identified global negative regulators of transcription in Saccharomyces cerevisiae. Mutant tsf3 strains exhibit defects in transcriptional silencing of the GAL1 promoter, allow expression from upstream activation sequence-less promoters, and exhibit pleiotropic defects in cell growth and development. Here we show that TSF3 is involved in transcriptional silencing mediated by the alpha 2 repressor and demonstrate that specific systems of transcriptional silencing may depend on the more global role of TSF3. Cloning and sequencing of TSF3 allowed us to predict a 974-amino-acid gene product identical to SIN4, a negative regulator of transcription of the HO (homothallism) mating type switching endonuclease. TSF3 disruptions are not lethal but result in phenotypes similar to those of the originally isolated alleles. Our results, together with those of Y. W. Jiang and D. J. Stillman (Mol. Cell. Biol. 12:4503-4514, 1992), suggest that TSF3 (SIN4) affects the function of the basal transcription apparatus, and this effect in turn alters the manner in which the latter responds to upstream regulatory proteins.

Amino Acid Sequence↗

Therapy of the occupationally injured hand and upper extremity.

This article orients the reader with the rationale and cost effectiveness of ergonomic tool design. Risk factors are identified, defined, and eliminated. Theoretic rationale for design principles provide the basis for intervention. The text offers specific tool design and adaptations for ease of application.

Arm Injuries↗

Ergonomic hand tool design.

The use of ergonomic design and appropriate selection of hand tools can reduce exposure to cumulative trauma. The design and principles presented in this article should help reduce the biomechanical stresses to the workers' hands, arms, and shoulders. Remember, tissues of each individual have a threshold of resistance, and if that threshold is crossed too many times by a defective or ill-fitting tool, pathologic changes can occur. The proper tool design, rotating work schedules, work pacing, scheduling, and exercise programs can, in combination, improve productivity and promote human wellness.

Arm Injuries↗

Post-traumatic tremor in head injured children.

In a survey of 289 severely head injured children the prevalence of significant tremor was estimated to be at least 45%. The tremor appeared at any time within the first 18 months after injury and in at least half the cases it subsequently subsided spontaneously. The implications of these findings are to question the mechanism of recovery and suggest that controlled trials of the treatment needed.

Adolescent↗

Residual chymopapain activity after chemonucleolysis in normal intervertebral discs in dogs.

Studies were carried out to demonstrate residual chymopapain activity in intervertebral discs after chemonucleolysis; protease assay, enzyme-linked immunosorbent assay, and immunohistochemical localization of the chymopapain in the disc tissue were done. Chymopapain, one milligram per level, was injected into the normal lumbar intervertebral discs of adult mongrel dogs and the discs were excised after two weeks. Proteolytically active chymopapain was still present in the extract of intervertebral disc at this time. The proteolytic activity was decreased by sulfhydryl inhibitors but not by inhibitors of metalloproteases or serine proteases. Protease and enzyme-linked immunosorbent assays showed that 0.60 +/- 0.48 per cent and 0.49 +/- 0.38 per cent of the original dose was present two weeks after the injection. Chymopapain was shown by immunohistochemical staining to be diffusely located throughout the extracellular matrix of the anulus fibrosus and the nucleus pulposus. Some cells, located mainly in the inner portion of the anulus, contained vacuoles filled with immunoreactive product.

Animals↗

The variability of young children's energy intake.

BACKGROUND: Research conducted in the 1930s showed that, given nutritious choices, children can select an adequate diet without adult supervision. Paradoxically, children grew well and were healthy despite patterns of intake at individual meals that were unpredictable and highly variable. METHODS: To investigate in more detail the energy intake of young children, we measured 24-hour food intake for 15 children, from two to five years of age, on six days. For each of the six days of the study, coefficients of variation were calculated for each child for each of the six meals and snacks (breakfast, lunch, dinner, and morning, afternoon, and evening snacks) and for total daily energy intake. RESULTS: The children's intake at individual meals was highly variable, but total daily energy intake was relatively constant for each child. The mean coefficient of variation for each child's energy intake at individual meals was 33.6 percent; in contrast, the mean coefficient of variation for each child's total daily energy intake was 10.4 percent. In most cases, high energy intake at one meal was followed by low energy intake at the next meal, or vice versa. CONCLUSIONS: Although children's food consumption is highly variable from meal to meal, daily energy intake is relatively constant, because children adjust their energy intake at successive meals.

Child↗

Area-based estimation of the initial volume of distribution and elimination rate constant following intravenous bolus injection.

We evaluate here an area term, the area under the rate of change of concentration-time curve (AURC), which allows the determination of the initial or central volume of distribution (V1). It has previously been shown that AURC is equal to the sum of the coefficients of a multiexponential equation and, therefore, V1 = dose/AURC. It is also shown that the normalized moment, AURC/AUC, is equal to the elimination rate constant, K10, where AUC is the area under the concentration-time curve. This area-based method to estimate V1 and K10 has been evaluated with simulation of three model equations and compared with nonlinear regression analysis of the same data. Random errors of 10 and 15% were introduced into the concentration values. The AURC method provides values of both parameters that are similar to those obtained from nonlinear regression analysis and which are reasonably accurate estimates of the theoretically correct values. The potential limitations of this area method are discussed. Good correlations were also observed for values of V1 and K10 obtained by AURC and regression methods for data obtained from the literature for 13 different drugs.

Female↗

Conditioned preferences: young children prefer flavors associated with high dietary fat.

In two experiments, 20 2-5-year-old children participated in a series of 8 conditioning trials to investigate whether they acquired conditioned preferences based on the fat content of a food. On different days, each child consumed fixed quantities of novelly flavored yogurts that were high or low in fat and energy density (220 or 110 kcal/serving). After conditioning, patterns of ad lib consumption data provided evidence of caloric compensation in response to the energy density differences in the preloads. Children consumed more following the low- than the high-fat preloads. Preference assessments, performed pre- and postconditioning, revealed conditioned flavor preferences based on fat content: children increased their preference for the high-density paired flavor, but no change in preference was noted for the low-density paired flavor. These data suggest that such conditioned flavor preferences based on energy density may be contributing to children's preferences for foods high in dietary fat.

Child, Preschool↗

Increase in sympathetic activity with age. I. Role of impairment of arterial baroreflexes.

The purpose of this study was to evaluate changes in arterial baroreflex function with aging. Mean arterial pressure (MAP) obtained in the awake state was 110 +/- 7 mmHg in the young animals (1 yr; n = 5) and 128 +/- 6 mmHg in the old beagles (11 yr; n = 11) (P less than 0.05). In response to bolus administration of varying doses of phenylephrine and nitroglycerin in the conscious state, the slope relating heart rate (HR) to MAP was attenuated significantly in the old animals compared with the young (-0.87 +/- 0.30 vs. -2.35 +/- 0.44 beats.min-1.mmHg-1; P less than 0.05). After atropine, the baroreflex control of HR was abolished in both groups. After anesthesia and sectioning of the aortic depressor nerves, and with isolated carotid sinus pressures (CSP) held at 50 mmHg, absolute renal sympathetic nerve activity (RSNA) was significantly greater in the old (368 +/- 40 Hz) vs. the young animals (41 +/- 9 Hz). In the old, the gains of baroreflex inhibition of MAP (0.78 +/- 0.09) and normalized RSNA (0.38 +/- 0.14%/mmHg) during increases in CSP were decreased significantly compared with the young (MAP, 1.16 +/- 0.17 mmHg, and RSNA, 0.72 +/- 0.06%/mmHg). In a subgroup of old normotensive animals (n = 5), the baroreflex gain of RSNA was still attenuated (0.43 +/- 0.11%/mmHg) compared with the young. The reflex reduction in absolute RSNA as a function of baseline RSNA was also impaired in old vs. young beagles.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Low levels of chromosomal mutations in germ cells derived from doxorubicin-treated stem spermatogonia in the mouse.

The mutagenic effects of doxorubicin (Adriamycin, ADR) on mouse spermatogonial stem cells were examined by analysis of spermatocyte chromosomes and of dominant lethality transmitted through the spermatozoa. The effects of ADR on mutations, cytotoxicity, and sperm head abnormalities were compared with those of radiation. The cytotoxic effect of 6 Gy of gamma-radiation on stem spermatogonia was equivalent to about 4-5 mg ADR/kg. Chromosomal translocations were observed in 0.6% of the spermatocytes of mice treated with ADR (2-6 mg/kg). In contrast, 6 Gy of radiation induced translocations in 11.1% of spermatocytes. No increase in dominant lethality was observed after treatment with ADR at doses up to 6 mg/kg, while the frequency after 6 Gy of radiation was 3.6%. Based on these results, ADR would be expected to be only a weak inducer of balanced chromosomal rearrangements. Because ADR at 4.5 mg/kg was much weaker than 6 Gy of gamma-radiation at inducing chromosomal translocations, but just as effective at inducing sperm head abnormalities, the level of sperm head abnormalities is not indicative of balanced chromosomal rearrangements induced in stem spermatogonia by cytotoxic agents.

Animals↗

The relationship of male transsexual typology to psychosocial adjustment.

In a search to uncover variables predictive of psychosocial adjustment of male transsexuals, this study examined features which have been empirically linked to characteristics of male transsexual typology. Data from 25 male transsexual volunteers were examined by means of multiple regression analysis to determine whether symptoms of introversion, depression, or tension, as well as adjustment to work and gender reorientation could be linked to the typological variables of androphilia, gynephilia, cross-gender fetishism, feminine gender identity in childhood, and age of onset of transsexualism. Valid and reliable scales measuring the typological variables of erotic partner preference (androphilia and gynephilia), cross-gender fantasy in association with sexual arousal (cross-gender fetishism), and degree of feminine gender identity in childhood were used. Results indicate a significant relationship between social gender reorientation and the feature of androphilia and between work adjustment and gynephilia. This differential adaptation is explained in terms of the different course that transsexualism takes within each typological subgroup. These findings offer evidence as to why some transsexuals may more readily adopt a female gender identity than others. There was no relationship found between the typological features and those variables measuring psychological disturbance.

Adult↗

Recovery of sperm production after chemotherapy for osteosarcoma.

Because treatment with surgery and combination chemotherapy produces a high cure rate in young men with osteosarcoma, their subsequent reproductive function is an important concern. Semen analyses of osteosarcoma patients, therefore, were performed before, during, and after treatment with the PADIC regimen consisting of cisplatin, Adriamycin (doxorubicin), and dacarbazine or, in some cases, the PADIC regimen plus additional drugs. Results showed that semen volume was not affected and that sperm motility was reduced only during treatment. Although nearly all patients were rendered azoospermic during treatment, sperm production resumed in 30 of 32 patients examined at least 2 years after treatment. Analysis with correction for censored data indicates that, in 78% of treated men, sperm counts will return to more than 10 million/ml. The percentage of men whose sperm counts recovered to normal was lower for those receiving cisplatin dosages greater than or equal to 600 mg/m2; no trends were observed with Adriamycin and dacarbazine dosages. The inclusion of additional drugs such as methotrexate, bleomycin, dactinomycin, or cyclophosphamide (less than 4 g/m2) did not significantly affect the recovery of spermatogenesis. We conclude that the risk of long-term infertility from treatment with the PADIC regimen is low.

Adolescent↗

Reactivity of the thiol groups of Escherichia coli phosphofructo-1-kinase.

Modification of Escherichia coli phosphofructo-1-kinase (6-phosphofructokinase; EC 2.7.1.11) with several thiol modifying reagents led to a pseudo-first-order loss of activity that was associated with the modification of a single cysteine residue, identified as the cysteine at position 119 in the protein sequence. This cysteine was protected from reaction with vinyl pyridine, bromopyruvate, and dithionitrobenzoic acid by the substrate, fructose-6-P. In the crystal structure of the highly homologous phosphofructokinase from Bacillus stearothermophilus, cysteine 119 is sufficiently distant from the catalytic site to exclude a direct steric inhibition of the binding of substrate as a mechanism of inactivation for the modification. Thus, the inhibition is unlikely to be a direct one but to be the result of interference with the conformational change that is associated with fructose-6-P binding. A second thiol, position 283, was shown to be protected from reaction when the enzyme was in its native conformation. In contrast to the previously published sequence for the E. coli enzyme six cysteines as opposed to seven have been found both in enzyme from strain LE392 and in enzyme produced by a plasmid that was derived from pLC 16-4. The position in question, 75, was identified as phenylalanine.

Chemical Phenomena↗

Pathogenesis of trachoma: the stimulus for inflammation.

Active trachoma is characterized by chronic inflammation of the conjunctiva, and repeated episodes of reinfection are thought to be necessary to sustain this inflammation. It is currently believed that much of the tissue damage is immunologically mediated. To identify which antigens might be responsible for stimulating this continued inflammation, cynomolgus monkeys that had recovered from a previous ocular infection with Chlamydia trachomatis were challenged with various antigen preparations. Purified preparations of formalin- or UV-inactivated elementary bodies did not elicit any inflammation even with daily inoculation. In addition, neither purified chlamydial major outer membrane protein nor lipopolysaccharide, including recombinant organisms expressing the lipopolysaccharide group antigen, elicit inflammation. A soluble triton extract of the organism rapidly induced marked inflammation when inoculated in the eyes of immune monkeys but had no effect in naive animals. These studies suggest that the continual inflammation in trachoma may not be due to repeated exposure to chlamydial surface antigen(s) but rather to a labile product released by the living organisms.

Animals↗

Xylose disposition in humans as a function of age.

D-xylose disposition was examined in 24 healthy men between 32 and 85 years of age. Xylose was administered as a 5 gm iv infusion and as a 25 gm po solution. Serum xylose concentrations and urinary excretion of intact xylose were determined. There were statistically significant inverse relationships with age for each of the following parameters after intravenous infusion: elimination rate constant (r2 = 0.71); systemic clearance (r2 = 0.66); renal clearance (r2 = 0.66); and nonrenal clearance (r2 = 0.35). Similar inverse relationships were found after oral dosing for the elimination rate constant (r2 = 0.69) and renal clearance (r2 = 0.54). There was no significant age relationship for the apparent volume of distribution or the steady-state volume of distribution. The percentage of the oral and intravenous dose recovered in urine up to 5 hours after dosing was significantly and inversely correlated with age. The implications of the latter finding are discussed with regard to the interpretation of the xylose tolerance test used to assess gastrointestinal absorptive capacity.

Administration, Oral↗