No abstract

To clarify mechanisms of hypothermia in lipopolysaccharide (LPS) shock, four experiments were conducted in 72 chronically instrumented Wistar rats. They were intended to accomplish the following: experiment 1, determine the dose of intravenous Escherichia coli LPS that induces a body temperature (Tb) fall at a minimal mortality [the dose chosen (0.5 mg/kg) was then used in experiments 2-4]; experiment 2, identify the time course of the arterial blood pressure (BP) fall (shock) during the response to LPS; experiment 3, measure threshold Tb values for skin vasodilation and activation of metabolic heat production (M) during the LPS shock; and experiment 4, ascertain behavioral thermoregulation in LPS shock. For experiments 1-3, rats were kept in restrainers; ambient temperature (Ta) was 26 degrees C. In experiment 4, rats freely moved in a thermogradient (18-33 degrees C). Variables monitored were colonic (Tc) and tail skin (Tsk) temperatures (experiment 1); BP (experiment 2); hypothalamic temperature (Thy), M (from oxygen consumption), and Tsk (experiment 3); and preferred Ta (Tpr) and abdominal temperature (experiment 4). In experiment 1, LPS induced no Tc changes at 0 mg/kg, a biphasic fever (no mortality) at 0.05 mg/kg, a biphasic hypothermia (42% mortality) at 0.5 mg/kg, and a rapid fall of Tc (100% mortality) at 5 mg/kg. LPS-induced (0.5 mg/kg) hypotension (experiment 2) occurred simultaneously with the first hypothermic phase; both Tc and BP reached their nadirs (-0.8 +/- 0.1 degrees C and -34 +/- 12 mmHg) at approximately 1.5 h post-LPS. The major autonomic mechanism of the shock hypothermia was a shift in the threshold Thy for M from 37.9 +/- 0.3 to 36.0 +/- 0.3 degrees C (experiment 3; P < 0.05). In experiment 4, rats selected Tpr below 25 degrees C (vs. 28-30 degrees C in control; P < 0.05) throughout the duration of the shock; their Tb dropped to 36.2 +/- 0.3 degrees C (P < 0.05). In sum, the LPS shock-associated hypothermia involves a decrease in the threshold Tb for M, the resultant widening of the interthreshold zone, and cold-seeking behavior.

No abstract

A new lung adenocarcinoma classification was recently proposed by IASLC/ATS/ERS. In this classification, invasive mucinous adenocarcinoma (IMC) is placed in a new category because of its unique radiologic, morphologic, and genetic characteristics. Minimal cytologic atypia characterizes this tumor; thus, it is occasionally difficult to make a diagnosis with a biopsy specimen. We used immunohistochemistry to examine HNF4α expression in a tissue microarray consisting of 278 lung adenocarcinoma specimens. In addition, we analyzed the clinicopathologic features, including EGFR, KRAS, and ALK mutation status. HNF4α expression was detected in 33 of the 37 surgically resected IMCs. The tumor cells were uniformly labeled with the molecule in all of the corresponding biopsy specimens, whereas the normal cells were not. Although HNF4α was also expressed in other lung adenocarcinoma subtypes, those with HNF4α expression shared IMC features, including negative TTF-1 expression (P<0.001), positive CDX2 expression (P<0.001), positive KRAS mutation status (P=0.001), and negative EGFR mutation status (P<0.001). Although some ALK-positive adenocarcinomas showed IMC morphology, the tumors were negative for HNF4α, suggesting that they belonged to a different group of tumors. We found that HNF4α labeled all of the IMC tumors except the ALK-positive adenocarcinomas. Thus, HNF4α positivity could serve as a useful marker for overcoming the diagnostic difficulties caused by minimal nuclear atypia and sparse tumor cells in small biopsy samples. Because other adenocarcinoma subtypes with HNF4α expression share clinicopathologic features with IMC, these adenocarcinomas, especially the columnar cell type of acinar-predominant adenocarcinoma, might constitute a biological spectrum of IMC.