Diaphragm activation with intramuscular stimulation in dogs

We studied in 10 supine anesthetized dogs diaphragm contraction produced by electrical activation with intramuscular electrodes surgically implanted in the ventral surface of the diaphragm and compared this with activation of the ipsilateral phrenic nerve (C5, 6, and 7) before it entered the thorax. Repetitive 40-Hz pulse trains with supramaximal current stimulus were used after hyperventilation of the animals to apnea. A single intramuscular electrode within 1 to 2 cm of the site of phrenic nerve entry into the diaphragm produced a mean transdiaphragmatic pressure of 12.0 cm H2O +/- 0.97 SE and mean tidal volume of 0.27 L +/- 0.04 SE. Mean values observed with phrenic nerve stimulation were not statistically different, and both electrode systems produced equivalent outward abdominal motion and upper rib cage paradox, as monitored by inductive plethysmography. There was no difference in gas exchange during stimulation with a single hemidiaphragm electrode and mechanical ventilation compared at the same tidal volume and respiratory rate. Blockade of neuromuscular transmission with curare eliminated intramuscular and phrenic nerve stimulation proportionately, suggesting that activation of the diaphragm is dependent in both cases on the phrenic nerve. This technique does not entail manipulation of the phrenic nerve and may have clinical application as an alternative technique for diaphragm pacing.     

Time of appearance and histology of tumors induced in the dorsal skin of C3Hf mice by ultraviolet radiation from a mercury arc lamp

The time course of skin tumor induction was determined in hair-clipped inbred agouti C3Hf mice irradiated three times per week with a medium-pressure quartz-mercury lamp; 4 different UV doses were used. Although the ears were also exposed to the radiation, in the 3 groups given the highest doses no ear tumors were observed by the time each animal had developed at least 1 tumor on its back. No tumors were found in the animals receiving the lowest UV dose. In the group receiving the highest dose, males developed tumors earlier than did females; this trend continued in the lower dose groups. Many tumors that developed in the back skin were well-differentiated squamous cell carcinomas. Others were less well-differentiated squamous cell carcinomas. Others were less well defined so that the cell of origin was difficult to determine. In the group receiving the highest UV dose, the squamous cell carcinomas were few, whereas at the lower doses they predominated.     

Basophilic blast crisis in chronic myeloid leukemia

Acute nonoliguric renal failure developed in a 13-year-old girl, 1 month after the institution of isoniazid therapy because of a positive tuberculin test at school screening. A renal biopsy demonstrated severe crescentic glomerulonephritis with focal interstitial changes. Discontinuation of isoniazid and a short course of steroids and cyclophosphamide therapy were followed by complete recovery. Whereas isoniazid has been shown to induce a lupus-like syndrome and antihistone antinuclear antibodies, our patient displayed none of the clinical or immunological features that are characteristic of drug-induced lupus. Furthermore, none of the identifiable causes for crescentic glomerulonephritis was evident in this girl. To the best of our knowledge this is the first report suggesting a possible association of crescentic glomerulonephritis to isoniazid treatment.     

Differential immediate early gene expression in conditional hepatitis B virus pX-transforming versus nontransforming hepatocyte cell lines

We report construction and characterization of tetracycline-controlled hepatitis B virus pX-expressing hepatocyte (AML12) cell lines. These cell lines were constructed in AML12 clonal isolates (clones 3 and 4), which express constitutively the tetracycline-controlled transactivator. Since pX is implicated in HCC, this immortalized hepatocyte model system was used to investigate the mechanism of pX in transformation. Clonal isolates of 3pX and 4pX lineages display conditional synthesis of pX mRNA and protein and a 2-fold increase in growth saturation density following tetracycline removal, implicating pX in monolayer overgrowth. Interestingly, only 3pX clones display pX-dependent anchorage independence. Clone 3 lineages express hepatocyte nuclear factor-1alpha and hepatocyte-specific marker genes; clone 4 lineages express hepatocyte nuclear factor-1beta and reduced levels of hepatocyte-specific marker genes, suggesting the importance of the differentiated hepatocyte in pX-mediated oncogenic transformation. Importantly, 3pX and 4pX lineages display differential expression of immediate early genes c-fos and ATF3. The pX-transforming 3pX lineage displays early, pX-dependent induction of ATF3 and prolonged induction of c-fos. The nontransforming 4pX cells display an absence of pX-dependent ATF3 induction and transient induction of c-fos. Our results support the direct link of pX expression to oncogenic transformation in 3pX lineage clones and underscore the advantage of this conditional cellular model system for studying mechanisms of pX-mediated oncogenesis.