Malignant transformation of NIH3T3 cells by overexpression of mot-2 protein

The murine mortalin genes, mot-1 and mot-2, are members of the hsp70 family of proteins and differ from each other by only two amino acid residues. Mot-1 is expressed in normal cells and has pancytosolic cellular distribution whereas mot-2 is found in the perinuclear region of immortal cells. We report here that a high level of expression of mot-2 protein resulted in malignant transformation of cells as analysed by anchorage independent growth and nude mice assays. A high level of protein expression is attributed to the 900 bp 3' untranslated region of the cDNA which does not have any transforming activity per se. Mortalin cDNA clones isolated from human transformed cells were also found to have transforming activity in similar assays and a high level of expression was apparent in some of the human immortalized cells that showed non-pancytosolic mortalin immunofluorescence. Taken together, the data suggest that nonpancytosolic mortalin may have a role in tumorigenesis.     

Distribution of myosin heavy chain isoforms in non-weight-bearing rat soleus muscle fibers

The effects of 14 days of spaceflight (SF) or hindlimb suspension (HS) (Cosmos 2044) on myosin heavy chain (MHC) isoform content of the rat soleus muscle and single muscle fibers were determined. On the basis of electrophoretic analyses, there was a de novo synthesis of type IIx MHC but no change in either type I or IIa MHC isoform proportions after either SF or HS compared with controls. The percentage of fibers containing only type I MHC decreased by 26 and 23%, and the percentage of fibers with multiple MHCs increased from 6% in controls to 32% in HS and 34% in SF rats. Type IIx MHC was always found in combination with another MHC or combination of MHCs; i.e., no fibers contained type IIx MHC exclusively. These data suggest that the expression of the normal complement of MHC isoforms in the adult rat soleus muscle is dependent, in part, on normal weight bearing and that the absence of weight bearing induces a shift toward type IIx MHC protein expression in the preexisting type I and IIa fibers of the soleus.     

Pulmonary and systemic fat embolization after medullary canal pressurization: a hemodynamic and histologic investigation in the dog

BACKGROUND: The potential to produce fat embolism may be important in determining the ideal method and timing of fracture treatment in patients with preexisting lung injury. METHODS: Four dogs underwent femoral and tibial canal reaming and pressurization. Blood gas samples were analyzed, and pulmonary arterial pressure was monitored at 1 and 72 hours. Animals were killed 72 hours postoperatively, and the lungs, kidneys, and brain were examined histologically and compared with equivalent specimens from four control dogs that had not undergone femoral and tibial canal reaming and pressurization. RESULTS: Postmortem, intravascular fat persisted for 72 hours after induction of pulmonary fat embolism. Mean PaO2 was unchanged from baseline at 72 hours after canal pressurization. Canal pressurization caused a sustained increase in pulmonary arterial pressure (p=0.02) for 1 hour after canal pressurization. The mean pulmonary edema score at 72 hours was 29+/-3. Only a scant polymorph infiltrate (zero to two polymorphs per high-power field) was present at any time. No hyaline membranes were seen at any time. The percentage area occupied by intravascular fat in the lungs was 0.0214+/-0.0058 at 72 hours. No signs of ischemia or inflammation were seen in either the cerebral or the renal specimens. CONCLUSION: This study is the first to show that intravascular fat persists in the lungs, kidneys, and brain for 72 hours after canal pressurization and, by itself, does not cause pathologic evidence of acute inflammation.     

Endothelial injury following experimental subarachnoid hemorrhage in rats: effects on brain blood flow

BACKGROUND: The leading cause of death and disability in patients suffering from aneurysmal subarachnoid hemorrhage (SAH) is cerebral vasospasm, a persistent, progressive, and often irreversible constriction of cerebral arteries. A wide array of pathological changes occur in cerebral arteries following SAH, with endothelial injury being the earliest and most consistent one. Since intact endothelium modulates many reflexes that influence vascular tone, damage to them may represent a significant contributor to cerebral vasospasm. METHODS: Changes in local cerebellar blood flow (LCBF) and pathological alterations in major cerebral arteries were studied and compared in rats at various time intervals following SAH. SAH induced by the subarachnoid injection of 0.3 ml of whole blood. Sham rats received a subarachnoid injection of 0.3 ml of isotonic saline. RESULTS: Except for an immediate but transient decrease, LCBF remained unchanged over a 3 day period following saline injection. Likewise, there were no pathological alterations in cerebral arteries of saline-injected rats. In contrast, the subarachnoid injection of whole blood produced significant changes in both LCBF and cerebral arteries. Within 30 minutes post-blood injection, LCBF became significantly decreased and remained so for 4 hours. However, within 24 hours, LCBF had returned to control levels where it remained for 3 days. Endothelial injury was observed in the basilar and middle cerebral arteries from 30 minutes through 4 hours, the same periods in which LCBF was significantly reduced. Within 24 hours, the time period in which LCBF had rebounded to control ranges, cerebral arteries showed no evidence of endothelial damage and resembled control cells. CONCLUSION: The results indicate a direct correlation between changes in LCBF and the structural integrity of endothelial cells in the early stages following SAH. The lack of chronically depressed LCBF (after 1 day) may be related to the quick structural repair of endothelium.     

Imaging features and clinical significance of perineural spread or extension of head and neck tumors

Perineural spread of head and neck tumors is a form of metastatic disease in which tumor disseminates to noncontiguous regions along the endoneurium or perineurium. Both computed tomography (CT) and magnetic resonance (MR) imaging can help detect perineural spread, although MR imaging is the modality of choice because of its multiplanar capability, its superior soft-tissue contrast, and the decreased amount of artifact from dental hardware. Perineural spread most commonly occurs in adenoid cystic carcinoma and squamous cell carcinoma. Nerve enlargement may lead to foraminal enlargement and, ultimately, to foraminal destruction, findings that are best seen at CT. Extension through the foramen ovale and involvement of the Meckel cave is best seen on coronal T1-weighted MR images, and nerve enhancement is best seen on fat-suppressed T1-weighted MR images. Other radiologic findings include obliteration of fat planes at foraminal openings, neuropathic atrophy, cavernous sinus enlargement, and replacement of the trigeminal subarachnoid cistern with soft tissue. The pathway of perineural tumor spread is predictable with knowledge of the pertinent cranial nerve anatomy; however, patients with radiologically or pathologically proved perineural spread may have normal nerve function at clinical examination. Therefore, it is imperative that the radiologist be familiar with both normal cranial nerve anatomy and the radiologic appearance and assessment of perineural tumor extension.     

Deactivation on Vehicle-Aged Diesel Oxidation Catalysts

This paper studies oxidation catalytic converters that were vehicle-aged in a diesel automobile. The deposition of several atoms (S, P, C, Si, Ca, Zn and Fe) was detected by several chemical analysis techniques. Moreover, AlPO₄ and Al₂(SO₄)₃ were identified by XRD. The catalytic performance of the aged catalysts with different mileages showed a similar degree of deactivation for CO and C₃H₆ oxidation. By contrast, laboratory sintering carried out on fresh catalysts revealed that it may have certain impact in the deactivation of diesel catalysts. Nevertheless, the possibility that the impact of chemical deposition on deactivation has a threshold value cannot be discarded.     

Pharmacokinetics of tablet huperzine A in six volunteers

AIM: To study pharmacokinetics of tablet huperzine A (Hup-A) in Chinese volunteers to help establishing its drug administration schedule. METHODS: For 6 volunteers after a single oral dose of 0.99 mg, drug concentrations in plasma were assayed by reverse phase high pressure liquid chromatography (HPLC) at 0.5, 0.75, 1.0, 1.25, 1.5, 2, 4, 6, 8, and 10 h. The pharmacokinetic parameters were calculated with a 3P87 program by computer. RESULTS: The time course of plasma concentrations conformed to a one-compartment open model with a first order absorption. The pharmacokinetic parameters were as follows: T 1/2ka = 12.6 min, T 1/2ke = 288.5 min, Tmax = 79.6 min, Cmax = 8.4 micrograms L-1, AUC = 4.1 mg L-1 min. CONCLUSION: Hup-A was absorbed rapidly, distributed widely in the body, and eliminated at a moderate rate.     

The carcinogenic potential of the gas phase of environmental tobacco smoke

Female strain A/J mice were exposed to unfiltered or HEPA-filtered environmental tobacco smoke (ETS). Total suspended particulates (TSP) in the full smoke exposure chamber was 78.5 mg/m3 and in the filtered smoke chamber 0.1 mg/m3; nicotine concentrations in the full and filtered smoke chamber were 13.4 and 3.1 mg/m3, respectively. Animals exposed to filtered ETS (6 h a day, 5 days a week) and killed after 5 months had a higher lung tumor incidence and multiplicity than controls maintained in filtered air, although the differences were not statistically significant. Animals exposed to filtered and full ETS and allowed to recover in air for 4 months had an average of 1.2 +/- 0.3 tumors per lung and 1.3 +/- 0.3 tumors per lung, respectively. Air exposed control animals had an average tumor multiplicity 0.5 +/- 0.1 tumors per lung. Increased immunostaining for CYP 1A1 was not evident in the lung of animals exposed to filtered smoke. Based on the chamber concentrations of selected nitrosamines and polycyclic aromatic hydrocarbons, the possible maximum uptakes by the mice of NNK, NNN and benzo[a]pyrene during the 5 months exposure period were three to six orders of magnitude below doses reported in the literature to produce 1 lung tumor in strain A/J mice. It was concluded that the gas phase of ETS is as carcinogenic as is full ETS. The carcinogenicity of the gas phase may be due to some as yet unidentified, yet highly potent carcinogens or by placing a substantial, possibly free radical-mediated oxidative stress on the lung.