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Biomedical subjects

B Stringer

Publications and source records attributed to B Stringer.

At least 19 recordsLinked to original sources

Endothelial type nitric oxide synthase in skeletal muscle fibers: mitochondrial relationships.

Immunohistochemistry shows that skeletal muscle fibers express endothelial-type (ec)-NOS in a heterogeneous pattern distinct from that of neuronal (nc)-NOS. Analysis of adjacent serial sections reveals: 1) a strong correlation of ec-NOS expression to mitochondrial content (visualized histochemically by succinate dehydrogenase); 2) lack of correlation of ec-NOS to fiber ATPase type (in contrast to nc-NOS); and 3) constitutive co-expression of ec- and nc-NOS in some fibers. Preparations of mitochondria from diaphragm exhibited calcium-dependent NOS activity, which functioned to inhibit in vitro oxygen consumption. The results establish that normal skeletal muscle cells can express two constitutive isoforms of NOS (nc- and ec-) and suggest a functional role for ec-NOS in oxidative, mitochondria-rich fibers.

Amino Acid Oxidoreductases

Flow cytometric assay of lung macrophage uptake of environmental particulates.

We sought to establish a quantitative method using flow cytometry to study uptake of environmental particulates by alveolar macrophages (AMs). We used right angle light scatter (RAS) to measure uptake of titanium dioxide, quartz, and diesel particulates. After incubation with TiO2 in vitro, AMs showed dose-dependent increases in both cell-associated particles visualized by microscopy and RAS measured by flow cytometry (e.g., fold increase RAS at 4, 8, 16, 32, and 80 micrograms/ml, respectively, = 2 +/- 0.1, 4.0 +/- 0.5, 5.5 +/- 0.5, 9.1 +/- 2.5, 14.3 +/- 0.9; mean +/- SEM). Similar results were obtained with quartz and diesel particles. A strong correlation was observed between particle load per cell and AM RAS after uptake of fluorescent latex beads or fluorescent TiO2 (coated with BODIPY-BSA) (R2 = 0.984, 0.997, respectively). Using this technique, we found AM uptake of environmental particulates to be substantially greater than that of a panel of myelomonocytic and epithelial cell lines, consistent with their physiologic role in pulmonary defenses. RAS measurements have also identified both calcium-dependent and calcium-independent components in AM interactions with inert particles. Although this technique does not allow precise quantitation of particle number or mass per cell, flow cytometric analysis of relative increases in RAS is a useful tool to study AM interactions with a variety of environmental particulates.

Animals

Differential regulation of primary response gene expression in skeletal muscle cells through multiple signal transduction pathways.

One of the earliest cellular responses to growth factors is the rapid induction of primary response genes. One group of such genes was originally isolated as tetradecanoyl phorbol acetate (TPA) inducible sequences (TIS genes) from mouse 3T3 cells. Proteins encoded by the TIS genes include two transcription factors: TIS8 (also known as egr1/NGFIA/zif268) and TIS1 (also known as NGFIB/nur77/N10). We have examined the inducibility of these two genes in a skeletal muscle cell line in response to agents that have been reported to block muscle differentiation. We report here that basic fibroblast growth factor (bFGF) induced the expression of both TIS1 and TIS8 in mouse C2C12cells. Both genes were also inducible by TPA while forskolin which activates the cAMP-dependent pathway induced TIS1 but not TIS8. Down-regulation of protein kinase C (PKC) activity by TPA pretreatment repressed the bFGF induction of TIS1 but had little effect on the bFGF-stimulated expression of TIS8. Moreover, while both TPA and bFGF stimulated the hyperphosphorylation of c-RAF and the activity of MAP kinase, TPA pretreatment failed to block RAF phosphorylation or the stimulation of MAP kinase activity by bFGF. Induction of the two TIS genes in skeletal myoblasts therefore appeared to be dependent to different extents on the activation of protein kinase A (PKA), PKC and MAP kinase.

Animals

A deadly design.

On September 30, 1991, registered nurse Bev Holmwood sustained a needlestick injury while working in a Vancouver Island operating room. Just over two months later she died, the result of hepatitis C she contracted during the accident. Her story is a sad reminder of what research has already shown: Sharps injuries are the single greatest cause of serious, and often deadly, infection among nurses and other health care workers.

Equipment Safety

A study of the use of gloves in a large teaching hospital.

A study was conducted in the wards and laboratory of a 900-bed teaching hospital to determine the appropriateness of glove use. In the wards the rate of appropriate use was 59%, and in the laboratory it was 90%. In general, in the patient areas gloves were used for specific tasks (70%) whereas in the laboratory use for a specific task was only 32%. Financial savings could be realized by educational programs in infection control directed toward a more rational use of gloves.

Attitude of Health Personnel

High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis.

Using polymerase chain reaction amplification and oligonucleotide probing, the activation of ras oncogenes in 24 benign and 20 malignant human thyroid neoplasms was examined. The frequency of ras oncogene activation was similar at all stages of tumorigenesis in this system, being found in 33% of adenomas overall (50% of microfollicular tumours), 53% of differentiated follicular carcinomas and 60% of undifferentiated carcinomas. This supports the contention that mutation of these oncogenes occurs at an early step in tumorigenesis. The predominant amino acid substitution in the differentiated tumours was glutamine to arginine at position 61 of Ha-ras or N-ras, but this mutation was not found in any of the undifferentiated tumours. It was noted that while transition mutations predominated in differentiated tumours (both benign and malignant), transversions were more common in the undifferentiated tumours.

Adenoma

Hepatitis.

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Cross Infection

Ornithine decarboxylase activity in the neonatal rat heart following prenatal exposure to ethylene glycol monomethyl ether.

In mammals, ornithine decarboxylase (ODC) activity is highest during periods of rapid cellular growth and development, and the normal pattern of ODC activity during this period is sensitive to chemical and drug exposure. The industrial solvent ethylene glycol monomethyl ether (EGME) is teratogenic to rats and mice, with the heart being particularly sensitive. Basal ODC activity and ODC activity following an isoproterenol challenge were used to assess heart function in 3-, 9-, 16- and 22-day-old offspring from dams treated with 25 mg/kg EGME by gavage on days 7-13 or 13-19 of gestation. Reproductive outcome was not affected by EGME and none of the offspring had gross physical abnormalities. Gestation length was prolonged by both EGME treatments, but the increase was statistically significant only in the group treated on days 7-13 gestation. ODC activity per mg protein was greatest in 3-day-old rats and dropped off sharply during the following 3 weeks. In 3-day-old rats exposed on days 7-13 of gestation, ODC activity was 54% of that found in controls. ODC activity was comparable to that in controls in 3-day-old rats exposed on days 13-19 of gestation. Isoproterenol increased ODC activity in all groups, but additional functional abnormalities were not revealed by the isoproterenol challenge.

Aging

Electrocardiographic study of rat fetuses exposed to ethylene glycol monomethyl ether (EGME).

The widely used industrial solvent ethylene glycol monomethyl ether (EGME) is teratogenic to rats and mice, inducing a variety of heart and major vessel abnormalities. In the present study, electrocardiography was used to evaluate heart function in day 20 rat (Sprague-Dawley) fetuses from mothers treated on gestation days 7-13 (sperm = day 1) with 0, 25, or 50 mg/kg EGME by gavage in 10 ml/kg water. The increased incidence of fetuses with cardiovascular malformations (primarily right ductus arteriosus and ventricular septal defect) and abnormal electrocardiograms (EKG) was dose dependent. The most prevalent EKG abnormality was a prolonged QRS wave. Mean QRS intervals were not significantly increased by EGME exposure, but there were significantly more litters in the 50-mg/kg EGME group that had one or more fetuses with QRS complexes of 40 msec or longer. The enhanced duration and the appearance of the aberrant QRS's suggested the presence of an intraventricular conduction delay in these fetuses. Heart rate and other EKG characteristics such as the P wave or P-R and Q-T intervals were not significantly affected by exposure to EGME. There did not appear to be an association between abnormal EKG's and fetal heart dysmorphology.

Animals

Effect of goitrogen administration on the circadian rhythm of serum thyroid stimulating hormone in the rat.

Adult male rats were fed a goitrogen, aminotriazole, for 74 days at a dose known to suppress thyroid function completely. At the end of this period, these animals along with matched controls were killed in groups of seven at 3 hourly intervals throughout a 24 hour period, and serum TSH, T3, T4 and albumin assayed. No significant circadian rhythms of T3, T4 or albumin were found in either, but a highly significant rhythm of TSH was demonstrated both in controls and goitrogen treated groups, with a diminished relative amplitude in the latter. The results indicate that a significant diurnal rhythm of serum TSH persists in the rat despite long-term blockade of thyroid hormone synthesis and that the existence of this rhythm is therefore independent of the presence of circulating T3 or T4.

Amitrole

Bone scintigraphy for neonatal osteomyelitis: simulation by extravasation of intravenous calcium.

Intravenously administered calcium gluconate has become increasingly popular in the treatment of neonatal tetany. Occasionally, extravasation results in cellulitis, leading to a clinical diagnosis of superimposed osteomyelitis. Osseous scintigraphy, as the accepted modality in the early detection of osteomyelitis, would tend to be used in this circumstance. This case illustrates a false-positive result, probably due to soft-tissue calcification.

Bone and Bones