Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer.

Akt, a Serine/Threonine protein kinase, mediates growth factor-associated cell survival. Constitutive activation of Akt (phosphorylated Akt, P-Akt) has been observed in several human cancers, including lung cancer and may be associated with poor prognosis and chemotherapy and radiotherapy resistance. The clinical relevance of P-Akt in non-small cell lung cancer (NSCLC) is not well described. In the present study, we examined 82 surgically resected snap-frozen and paraffin-embedded stage I to IIIA NSCLC samples for P-Akt and Akt by Western blotting and for P-Akt by immunohistochemistry. P-Akt protein levels above the median, measured using reproducible semiquantitative band densitometry, correlated with a favorable outcome (P = 0.007). Multivariate analysis identified P-Akt as a significant independent favorable prognostic factor (P = 0.004). Although associated with a favorable prognosis, high P-Akt levels correlated with high tumor grade (P = 0.02). Adenocarcinomas were associated with low P-Akt levels (P = 0.039). Akt was not associated with either outcome or clinicopathologic variables.Cytoplasmic (CP-Akt) and nuclear (NP-Akt) P-Akt tumor cell staining was detected in 96% and 42% of cases, respectively. Both CP-Akt and NP-Akt correlated with well-differentiated tumors (P = 0.008 and 0.017, respectively). NP-Akt also correlated with nodal metastases (P = 0.022) and squamous histology (P = 0.037).These results suggest P-Akt expression is a favorable prognostic factor in NSCLC. Immunolocalization of P-Akt, however, may be relevant as NP-Akt was associated with nodal metastases, a known poor prognostic feature in this disease. P-Akt may be a potential novel therapeutic target for the management of NSCLC.     

Measurement of Carboxyhemoglobin and Methemoglobin by Pulse Oximetry: A Human Volunteer Study

Background: A new eight-wavelength pulse oximeter is designed to measure methemoglobin and carboxyhemoglobin, in addition to the usual measurements of hemoglobin oxygen saturation and pulse rate. This study examines this device's ability to measure dyshemoglobins in human volunteers in whom controlled levels of methemoglobin and carboxyhemoglobin are induced.

Methods: Ten volunteers breathed 500 ppm carbon monoxide until their carboxyhemoglobin levels reached 15%, and 10 different volunteers received intravenous sodium nitrite, 300 mg, to induce methemoglobin. All were instrumented with arterial cannulas and six Masimo Rad-57 (Masimo Inc., Irvine, CA) pulse oximeter sensors. Arterial blood was analyzed by three laboratory CO-oximeters, and the resulting carboxyhemoglobin and methemoglobin measurements were compared with the corresponding pulse oximeter readings.

Results: The Rad-57 measured carboxyhemoglobin with an uncertainty of +/-2% within the range of 0-15%, and it measured methemoglobin with an uncertainty of 0.5% within the range of 0-12%.     

A three-year prospective study of systemic manifestation in rheumatoid arthritis

Clinical Rheumatology - Rheumatoid arthritis (RA) as a systemic disease can attack many other organs in addition to the joints. A variety of pathological lesions of the blood vessels are...     

Cytomorphometric analysis of vaginal cells during normal cycle, under oral contraceptive therapy or in-vitro fertilization stimulation protocol

A cytomorphometric analysis of superficial vaginal cells inwomen in three groups of different types of hormonal concentrationwas made. There were 15 women in each group. Group I was studiedduring a natural cycle, group II under oral contraceptive therapyand group III during an in-vitro fertilization (IVF) stimulationprotocol. Morphometric parameters were measured on an imageanalyser. The area, perimeter and several form factors weremeasured separately for nuclei and cytoplasm. The nucleus:cytoplasmicratio was also determined. The cytoplasmic area was significantlyreduced in group II and was associated with a statisticallysignificant reduction of the nuclear area. The nucleus:cytoplasmicratio appeared significantly increased in group II and reducedin group III. Low oestradiol impregnation obtained with an oralminidosed contraceptive interfered with vaginal cell maturation.High oestradiol concentrations obtained during IVF protocolsinduced marked nuclear pycnosis but did not induce supra-physiologicalcell enlargement. Maximal cell size is genetically regulatedaccording to Driesch's law of volume invariance and hormonalover-stimulation has no effect on cell size. The nucleus:cytoplasmicratio appears to be a powerful parameter reflecting the oppositeeffects of hormones on cell compartments.     

Effects of baclofen and phaclofen on receptive field properties of rat whisker barrel neurons

Extracellular single-unit recordings were made in somatosensory cortical barrels of fentanyl-sedated rats. Whiskers were deflected singly or in paired combinations. lontophoretically-applied (−)-baclofen disproportionately reduced weak responses, and phaclofen disproportionately increased them, resulting in more tightly focused or more broadly focused receptive fields, respectively. Both drugs had only minor effects on surround inhibition. In light of previous findings, we conclude that GABA_A and GABA_B mechanisms both act to enhance spatial contrast, but that the former plays a much greater role in enhancing temporal resolution.     

Alteration of cytochrome P-450 by prolonged administration of imipramine and/or lithium to rats

Summary The aim of this study was to investigate imipramine-induced alterations of cytochrome P-450 and to determine whether prolonged concomitant administration of imipramine and lithium results in a pharmacokinetic interaction.Male Wistar rats received imipramine (10 mg/kg i. p.) at 12 h intervals or lithium chloride (100 mg/kg in drinking water) or they were treated with the combination of these drugs for 2 weeks. The long term treatment with imipramine produced a very complex alteration of cytochrome P-450: imipramine increased the level of the cytochrome, but it decreased the rate of its own aromatic hydroxylation in position 2. The rate of N-demethylation in the side chain was not changed. Consequently, in the case of both hydroxylation and demethylation, calculated molecular activities were decreased to 48% and 70% respectively. This differential change in activities corresponded well to the observed decrease of absorption in difference spectra (type I) produced in microsomes by imipramine. Carbamazepine-induced type I difference spectra were also decreased by imipramine pretreatment, but to a lesser extent. In contrast, hexobarbital type I binding was increased by imipramine treatment while type II difference spectra produced by metyrapone were not affected. The preliminary SDS-PAGE analysis of cytochrome P-450 isoenzymes of control and imipramine treated rats showed that the investigated antidepressant markedly intensified a protein band at 50.11 kD while bands at 51.28 kD, 56.20 kD and 56.88 kD were less intensive. These results indicate that the alteration of cytochrome P-450 by imipramine treatment is not only of quantitative but also of qualitative character. Lithium alone given to rats affected neither the concentration of cytochrome P-450 in microsomal protein nor the rate of imipramine metabolism in vitro. Lithium given jointly with imipramine reduced imipramine-induced elevation of cytochrome P-450. This, however, did not cause any change in the rate of imipramine metabolism in vitro and accordingly in imipramine pharmacokinetics in vivo. The concentration of lithium in the blood plasma tended to increase by concurrent administration of imipramine.Send offprint requests to K. J. Netter at the above address