CHFR expression is preferentially impaired in smoking-related squamous cell carcinoma of the lung, and the diminished expression significantly harms outcomes

Loss of tumor suppressors and activation of oncogenes lead to carcinogenesis. Abnormal expression of CHFR, a novel checkpoint gene, or of Aurora kinases, key regulators of mitosis, has been detected in a variety of solid tumors. Recently, CHFR has been revealed to ensure chromosomal stability by controlling the expression level of Aurora-A in vitro. However, the frequency of aberrant expression of these proteins and the association with clinicopathologic parameters remain poorly defined in nonsmall-cell lung cancer (NSCLC). In this study, we investigated the immunohistochemical protein expression of CHFR and Aurora-A in 157 NSCLC cases and evaluated the association between clinicopathologic parameters statistically. The relationship between CHFR protein and mRNA levels and the association between this relationship and promoter methylation of the CHFR gene were also examined in 20 frozen sections of NSCLC. Overexpression of Aurora-A and reduced expression of CHFR were found in 94 cases (59.8%) and 62 cases (39%) of NSCLC, respectively, and those were significantly correlated with tumor differentiation and size. Moreover, diminished CHFR expression was significantly associated with smoking-related squamous cell carcinoma cases and poor prognosis. Multivariate analysis revealed that CHFR expression was an independent prognostic factor. A statistical correlation was evident between CHFR protein and mRNA expression. In conclusion, our results suggest the aberrant expression of Aurora-A and/or of CHFR contributed to the increase in the malignant potential of NSCLC. We also revealed that CHFR expression was predominantly impaired in smoking-related squamous cell carcinoma and might be a useful prognostic marker in NSCLC.     

Transventricular mitral valve replacement in a patient with a left ventricular aneurysm: Report of a case

(Received for publication on Dec. 18, 1996; accepted on July 8, 1997)     

Loss of serum HCV RNA at week 4 of interferon-α therapy is associated with more favorable long-term response in patients with chronic hepatitis C

To determine the virological factors associated with a favorable long-term response to interferon-α (IFN) therapy in chronic hepatitis C virus (HCV) infection, 61 Japanese patients with chronic HCV infection were treated with IFN for 24 weeks (780 million units in total) and followed for 8 to 16 months after cessation of therapy. Ten patients dropped out because of severe side effects. Of the 51 patients who completed IFN therapy, 23 showed complete and sustained response (CR→SR), 13 complete response with early relapse (CR→Rel), and 15 no response to IFN (NR). For the pretreatment serum HCV RNA level, 20/23 who had CR→SR had <l0⁶ eq/ml compared to 3/13 CR→Rel and 1/15 NR (P< 0.01). Serologically defined HCV type 2 infection was also associated with a better opportunity to develop CR→SR compared to CR→Rel of NR (P<0.01). Loss of serum HCV RNA at week 4 of IFN therapy was also associated with a more favorable long-term response [17/19 CR→SR were HCV RNA negative compared to 3/11 CR→Rel (P<0.01)and2/13NR(P<0.01)]. n contrast, normalization of serum alanine ami-notransferase (ALT) levels at week 4 was found in 9/19 CR→SR compared to 8/11 CR→Re1 (P= NS), and 0/13 in NR (P<0.01). Six months after cessation of IFN therapy, 3/25 CR→SR patients were HCV RNA positive despite normalization of serum ALT levels. These data indicated that in addition to pretreatment serum HCV RNA levels and HCV type, the kinetics of response to IFN (at week 4) were also predictive of subsequent long-term response to IFN in patients with chronic HCV infection. © 1995 Wiley-Liss, Inc. © 1995 Wiley-Liss, Inc.     

Hypothermia inhibits the alveolar epithelial injury caused by hyposmotic albumin solution during preservation of the resected human lung

This study was conducted to determine whether hypothermia inhibited alveolar epithelial injury in the resected human lung during preservation. Hyposmotic albumin solution, 248mOsm/kg, was instilled into the alveolar spaces of resected human lungs which were inflated with an airway pressure of 7 cmH₂O and stored at either 37°C or 8°C for 4h. Alveolar fluid was aspirated and the influx of lactate dehydrogenase (LDH) and globulin into the alveolar spaces, as markers of alveolar epithelial injury, was measured. Ion transport and fluid clearance across the alveolar epithelium were calculated by the changes in electrolyte and albumin concentrations in the alveolar fluid, respectively. While the LDH levels and globulin concentrations increased significantly in the hyposmotic experiments at 37°C, hypothermia inhibited these increases. Alveolar fluid clearance at 37°C increased to 20% in the hyposmotic experiments compared with 12% in the control isosmotic experiments; however, sodium and chloride transport in the hyposmotic experiments was not significantly different from that in the isosmotic experiments. Thus, we conclude that hypothermia at 8°C inhibits alveolar epithelial injury caused by the hyposmotic solution in resected human lungs. Moreover, alveolar ion and fluid clearance mechanisms were preserved across the injured alveolar epithelial cells.     

Inhibitory effect of a novel angiotensin II type 1 receptor antagonist RNH-6270 on growth of vascular smooth muscle cells from spontaneously hypertensive rats: different anti-proliferative effect to angiotensin-converting enzyme inhibitor.

The current study was undertaken to evaluate the anti-proliferative effect of a novel angiotensin II type 1 (AT1) receptor antagonist, RNH-6270, on exaggerated growth of vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR), in comparison with the effects of an angiotensin-converting enzyme (ACE) inhibitor. RNH-6270 and temocapril significantly inhibited basal DNA synthesis in VSMCs from SHRs in a dose-dependent manner, but not in cells from Wistar-Kyoto (WKY) rats. SHR-derived VSMC showed a hyperresponse of DNA synthesis to serum and angiotensin II compared with that of WKY rats-derived VSMC. RNH-6270 did not affect serum-stimulated DNA synthesis in VSMCs from both rat strains. RNH-6270 abolished angiotensin II-stimulated DNA synthesis in VSMC from both rat strains. RNH-6270 significantly inhibited proliferation of VSMC from both rat strains, but the ACE inhibitor temocapril did not exert such an effect. RNH-6270 decreased the specific binding of angiotensin II to VSMC in a competitive manner for angiotensin II receptors in both rat strains. RNH-6270 and temocapril significantly decreased the expression of growth factor mRNAs and proteins in VSMC from SHR, but not in cells from WKY rats. These results suggest that RNH-6270 is a potent AT1 receptor antagonist and has anti-proliferative effects on VSMCs from SHR, which was not seen with an ACE inhibitor. The growth inhibitory effect of RNH-6270 may be associated with the inhibition of growth factors via antagonism to AT1 receptors.     

Influence of O6-methylguanine-DNA methyltransferase activity on chloroethylnitrosourea chemotherapy in brain tumors

Chloroethylnitrosoureas (CENUs) alkylate DNA at specific sites and inhibit DNA replication in tumor cells. O⁶-Alkylguanine moieties resulting from alkylation of guanine bases are thought to be one of most lethal adducts in living cells. Effectiveness of CENUs is known to relate well with an enzymic activity of the DNA repair enzyme O⁶-methylguanine-DNA methyltransferase (MGMT), which recognizes and removes O⁶-alkylguanine. To improve therapeutic results of CENUs, we have measured MGMT activity of human brain tumors and studied the relationship between MGMT activity and clinical responsiveness to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU). Thirty-seven patients with brain tumors were entered into the study. The neoplasms included gliomas, non-glial tumors, and brain metastases. The MGMT activity of gliomas was significantly lower than that of non-glial tumors and brain metastases. No significant difference in the enzyme activity was noted between low- and high-grade gliomas. Out of the 22 gliomas 5 tumors indicated a value below 60 fmol/mg, suggestive of a methyl excision repair minus (Mer^?) tumor. Two out of 3 evaluable patients with a Mer^? tumor responded well to post-operative ACNU adjuvant chemotherapy. Our results suggest that brain tumors include a certain percentage of Mer^? phenotype tumors, and that CENUs such as ACNU should be applied selectively on tumors with a low MGMT activity in order to increase the therapeutic effectiveness. © 1993 Wiley-Liss, Inc.     

Survival and clinical results of a modified &quot;<Emphasis Type="Italic">crosse de hockey</Emphasis>&quot; procedure for chronic isolated patellofemoral joint osteoarthritis: mid-term follow-up

Background

The optimum treatment for isolated patellofemoral joint osteoarthritis (PFJ-OA) remains controversial. The aim of this study was to assess the mid-term clinical results of a modified crosse de hockey procedure for the treatment of isolated PFJ-OA.

Materials and methods

We assessed 37 knees in 31 patients treated by a modified crosse de hockey procedure. The mean age was 57.6 years (range, 46–75 years) and mean follow-up was 90.1 months (range, 24–216 months). We evaluated clinical and radiographic outcomes, as well as complication rates at the mid-term follow-up.

Results

The Kujala score (mean improvement of 46.7, P < 0.001) and the Fulkerson score (mean improvement of 19, P = 0.001) were significantly higher compared to preoperative values. Overall clinical results rated excellent in 24.3 %, very good in 21.6 %, good in 35.1 %, fair in 13.5 %, and poor in 5.4 % of knees. Patellar tilting (P = 0.015) and congruence angle (P = 0.018) significantly improved postoperatively. On the other hand, the Insall-Salvati index decreased at the time of follow-up, although it remained in the physiologic range. Postoperatively, consecutive disease progression in the tibiofemoral joint and patellofemoral joint osteoarthritis were 18.9 and 5.4 %, respectively. The operative complication rate was 5.4 % in this case series. These percentages were lower than those of alternative tibial tuberosity osteotomy techniques.

Conclusion

In most patients with chronic isolated PFJ-OA, tibial tuberosity osteotomy by modified crosse de hockey is a reliable procedure that provides good/excellent mid-term clinical results.

Level of evidence

Level IV.

     

Quantitative analysis of the Trendelenburg test and invention of a modified method

Background

While the Trendelenburg test has been used for 120 years to detect hip abductor muscle weakness, the methodology has not been standardised.

Laboratory evaluation of heat-and-moisture exchangers

We conducted a laboratory study on six commercially available heat and moisture exchangers in order to determine and compare their water retaining efficiency and their contribution to airway resistance.The Gambro-Engström Edith Flex device was the most desirable of the six devices we evaluated in terms of its water retaining efficiency. The NMI Pneumoist 1 and the Siemens Servo Humidifier 153 units had good water retaining capacity but their higher airflow resistance need close monitoring, especially after prolonged clinical use. The Pall HME 15–22 and the Portex Humid-Vent 1 devices were also efficient in water retaining capacity. The Pall also demonstrated low airflow resistance and the minimum increase in airflow resistance after water immersion. The pathogen filtering capacity of the Pall should also be considered an additional advantage, especially in infected patients. The Terumo Breathaid device performed worst of all six devices, but it was still better than no HME at all.(Kugimiya T, Phuc TG, Numata K: Laboratory evaluation of heat-and-moisture exchangers. J Anesth 3: 80–85, 1989)