The prognostic value of p53, Ki-67 and matrix metalloproteinases MMP-2 and MMP-9 in transitional cell carcinoma of the renal pelvis and ureter

AIM: To investigate the prognostic and predictive relevance of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 in patients with transitional cell carcinoma (TCC) of the upper urinary tract. METHODS: The expression of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 was examined by immunohistochemistry in 69 patients with TCC of the upper urinary tract. Correlation of p53, Ki-67, MMP-2 and MMP-9 over-expression with conventional pathological parameters and patient survival was examined. RESULTS: p53 over-expression was significantly correlated with histological grade (P < 0.05), but not with pathological stage, vascular invasion, lymphatic invasion or lymph node metastasis. Ki-67 over-expression was significantly correlated with stage, grade, lymphatic invasion and vascular invasion (P < 0.05). In survival analyses, Ki-67 over-expression was a significant prognostic factor in the univariate analysis (P < 0.05), but it did not have a significant impact on survival in the multivariate analysis. Ki-67 labeling index was a significant prognostic factor in patients with a low p53 labeling index, but not in patients with a high p53 labeling index. CONCLUSION: Ki-67 over-expression is of prognostic value in TCC of the upper urinary tract, while p53, MMP-2 and MMP-9 are of limited value.     

Alteration in immunoexpression of glucose transporter 2 in liver of tumour-bearing rats

To elucidate interactions between the glucose transport system and hepatic glucose production in the tumour-bearing state, glycogen storage, expression of glucose transporter isoform 2 (Glut 2) and activities of glucose-6-phosphatase (G-6-Pase) and hexokinase were histochemically examined in hepatocytes of tumour-bearing rats. Five male F344 rats, subcutaneously inoculated with methylcholanthrene(MCA)-induced sarcoma cells were compared with five pair-fed animals and four ad libitum fed controls. Glycogen storage was markedly decreased in liver cells of tumour-bearing rats compared to in those of control animals. Glut 2 immunoreactivity was uniformly seen in the cellular membrane of hepatocytes from control animals. In rats bearing sarcoma, the staining intensity was significantly decreased, suggesting that Glut 2 with its bi-directional transport capacity was down-regulated in the tumour-bearing state. Positive staining for hexokinase activity was located in the perivenous area in livers from control animals and was more diffusely located and more intense in livers from tumour-bearing animals. G-6-Pase activity, limited to the peripheral area in livers from controls, extended to the intermediate area and had stronger reactivity in livers from tumour-bearing animals. In the tumour-bearing cachectic condition, glucose may be partially consumed by a futile cycle, hepatic metabolic zonation was disturbed, and the release of glucose from the liver may not be mediated by a facilitative glucose transporter-2.     

Enhancing Effects of Unsaturated Fatty Acids with Various Structures on the Permeation of Indomethacin through Rat Skin

Effects of straight-chain, cis-type, unsaturated fatty acids with various structures (alkyl chain lengths, numbers of double bonds, position of double bonds and cis- and trans-positional isomers) on the skin permeation of indomethacin were examined by using rat skins in-vitro. Furthermore, the disordering degrees of the intercellular lipid domain in the stratum corneum, which were treated with preparations of unsaturated fatty acids, were measured by the Fourier transform infrared (FT-IR) method using excised rabbit ear skins. Unsaturated fatty acids enhanced the permeation of indomethacin through rat skins. These permeation-enhancing effects by unsaturated fatty acids were affected by changes of their alkyl chain length from C₁₄ to C₂₂. The lag-times on the permeation of indomethacin were shortened by unsaturated fatty acids in the following order: C₂₀ = C₁₈ = C₂₂ < C₁₆ < C₁₄. These fluxes were increased by unsaturated fatty acids in the following order: C₂₀ > C₂₂ = C₁₈ = C₁₃ > C₁₄. Therefore, gondoic acid (cis-11-eicosenoic acid; C₂₀H₃₈O₂) mostly enhanced the skin permeation of indomethacin. However, the enhancing effects of unsaturated fatty acids (C₁₈ chain) were not affected by their differences of position and numbers of double bonds. These permeation-enhancing effects which were evaluated by flux were related to the degrees of wave-number shift in the frequency of the antisymmetric CH bond stretching absorbance (near 2920 cm^?1) on FT-IR spectra of the fatty acid-treated stratum corneum. Therefore, the perturbation increase of lipid domain in the stratum corneum by these fatty acids probably was the cause of the enhancing effects of permeation of indomethacin.     

A case of X-linked α-thalassemia/mental retardation syndrome: Analysis of hemoglobin by an automated glycated hemoglobin analyzer

A 5-year-old male patient with X-linked α-thalassemia/mental retardation syndrome is reported. He showed multiple minor anomalies including characteristic facial abnormalities, α-thalassemia, severe mental retardation, and hypogonadism. Analysis of his hemoglobin by high performance liquid chromatography using an automated glycated hemoglobin analyzer revealed an abnormal peak. Identification of an abnormal peak by an automated glycated hemoglobin analyzer will aid in the diagnosis of patients with X-linked α-thalassemia/mental retardation syndrome.     

Outbreak of acute glomerulonephritis in children: Observed association with the T1 subtype of group A streptococcal infection in Northern Kyushu,Japan

Group A streptococcal infection is associated with the occurrence of acute glomerulonephritis (AGN) and rheumatic fever (RF). A surveillance study in the Saga area, in northern Kyushu, Japan, showed a small variation in the reported number of group A streptococcal infections in the period 1988–94. However, of the AGN cases reported in this period, more than half were observed in 1992. In order to examine whether some change had occurred in the serotype distribution of Streptococcus pyogenes during the period, patients in the Saga area diagnosed as having group A streptococcal infection and patients with AGN or RF were analyzed. Serological T-typing of S. pyogenes was carried out for patients with group A streptococcal infections, and the association between the occurrence of AGN or RF and the distribution of each different T subtype was analyzed. M-typing of S. pyogenes was also carried out and the correlation between T and M types was examined. From 1988 to 1994, the annual number of patients with group A streptococcal infections in the Saga area showed a small variation, range 65–100 patients/year. Of the 42 patients with AGN and three with RF observed in this period, 27 with AGN (64%) and one with RF (33.3%) were detected in 1992. Only the T1 subtype increased in 1992; the other T subtypes showed little variation in incidence. The number of patients with the T1 subtype was significantly correlated with the occurrence of AGN by regression analysis (P < 0.01). Of the 170 subjects tested for both T and M subtypes, 44 of the 45 T1-typed subjects had the M1 protein. Our epidemiological study suggested that the T1 subtype of streptococcal infection was associated with an outbreak of AGN in 1992 in the Saga area.     

Biatrial Epicardial Pacing Prevents Atrial Fibrillation and Confers Hemodynamic Benefits After Coronary Artery Bypass Surgery

Biatrial pacing (BIP) can be more effective than standard right atrial pacing (RAP) in preventing atrial fibrillation (AF) after coronary artery bypass graft surgery (CABG). However, the mechanisms and hemodynamic benefits of BIP have not been studied in detail. This study examined the efficacy and hemodynamic benefits conferred by overdrive epicardial BIP in preventing post-CABG AF. After undergoing CABG, 72 patients (mean age = 66 ± 12 years, 48 men) were randomly assigned to triggered BIP (BIP-AAT; n = 50) versus single RAP (RAP-AAI; n = 22). The hemodynamic effects of BIP were measured by right heart catheterization and echocardiography. The patients were monitored for 8.8 ± 2.4 days after CABG to detect episodes of AF. The incidence of AF was significantly lower in the BIP-AAT group (22.0%) than in the RAP-AAI group (59.1%, P < 0.01). Cardiac output was significantly higher and pulmonary artery wedge pressure (PAWP) significantly lower during BIP-AAT than during RAP-AAI. The E-wave (65.2 ± 37.8 vs 57.8 ± 37.8 cm/s, P < 0.05) was significantly higher during BIP-AAT, and the interval between atrial pacing spike and the end of A-wave (241 ± 18.4 vs 286 ± 17.2 ms, P < 0.001) was significantly shorter during BIP-AAT than during RAP-AAI. Triggered BIP was well tolerated and significantly reduced the incidence of post-CABG AF compared to single-site RAP. The hemodynamic improvements conferred by BIP-AAT were due to a shortening of the inter-atrial conduction delay and greater contribution of left atrial contraction. These hemodynamic benefits may play a role in lowering intra-atrial pressure and in preventing AF.     

Action of human interleukin-4 and stem cell factor on erythroid and mixed colony formation by peripheral blood-derived CD34+c-kithigh or CD34+c-kitlow cells

We studied the interaction of interleukin (IL)-4 and other burst-promoting activity (BPA) factors, such as IL-3, granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-9 and stem cell factor (SCF), on erythroid burst-forming unit (BFU-E) and erythrocyte-containing mixed (CFU-Mix) colony formation in serum-free culture. IL-4 alone did not support mixed colony formation in the presence of erythropoietin (Epo). However, IL-4 showed weak but significant BPA when peripheral blood (PB)-derived CD34⁺c-kit^low cells were used as the target population. The BPA of IL-4 was much weaker than that of IL-3, which exerted the most potent activity, as previously reported. When CD34⁺c-kit^high cells were used as the target, four factors known to have BPA, IL-3, GM-CSF, IL-9 and SCF, could express BPA. In contrast, IL-4 alone failed to support erythroid burst formation. Interestingly, IL-4 showed a remarkable enhancing effect with SCF in promoting the development of erythroid burst and erythrocyte-containing mixed colonies from CD34⁺c-kit^low and CD34⁺c-kit^high cells. Delayed addition of SCF + Epo or IL-4+Epo to the cultures initiated with either IL-4 or SCF alone clearly demonstrated that SCF was a survival factor for both BFU-E and CFU-Mix progenitors. In contrast, the survival effect of IL-4 was much weaker than that of SCF, and appeared to be more important for progenitors derived from CD34⁺c-kit^low cells than for those derived from CD34⁺c-kit^high cells. It was recently reported that CD34⁺c-kit^low cells represent a more primitive population than CD34⁺c-kit^high cells. Taken together, these results suggest that IL-4 helps to recruit primitive progenitor cells in the presence of SCF.     

Pharmacological Studies on Puerariae flos III: Protective Effects of Kakkalide on Ethanol-induced Lethality and Acute Hepatic Injury in Mice

Kakkalide, one of the major isoflavonoid components of Puerariae flos, has been investigated for its effect on ethanol-induced intoxication and on hepatic injury, including hyperglycaemia, in mice. Kakkalide reduced mortality associated with administration of ethanol. At doses of 100 and 200 mg kg^? the effect of kakkalide was significant. The same dose of kakkalide prevented increased serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activity. At a dose of 200 mg kg^? it also counteracted ethanol-induced elevation of glucose levels. These results suggest that kakkalide might be useful for counteracting the effects of alcohol and might be effective for treating hepatic injury.     

Recovery of health related quality of life after radical prostatectomy in Japanese men: A longitudinal study

BACKGROUND: We performed a longitudinal survey of health related quality of life (HRQOL) after radical retropubic prostatectomy (RP) in Japanese men with localized prostate cancer. METHODS: The present study started with self-reported HRQOL assessments provided by 72 patients who received only RP. The RAND 36-Item Health Survey and the University of California, Los Angeles Prostate Cancer Index were administered before and 3, 6 and 12 months after RP. RESULTS: Patients who underwent RP showed problems in some domains of general HRQOL, but these problems diminished over time. Urinary function declined substantially at 3 months and continued to recover at 6 and 12 months, but scored lower than the baseline. Urinary bother at 3 months had a significant decrease, but at six months it turned out to be the same as the baseline. The data of sexual function and bother showed a substantially lower score after RP. The sexual bother score of the younger men was significantly worse than that of the older men. Those who underwent nerve sparing procedures experienced significantly better recovery of urinary and sexual functions than the non-nerve sparing group. CONCLUSION: Despite reports of problems with sexuality and urinary continence, general HRQOL was mostly unaffected by RP after 6 months. Although there was a substantial decrease in urinary function, recovery from urinary bother was rapid. Deterioration of the sexual domain was remarkable throughout the postoperative period. Therefore, careful attention should be given to preoperative counseling, especially for younger patients.