Effects of added bioactive glass on the setting and mechanical properties of resin-modified glass ionomer cement

In this study, the effects of added bioactive glass on the basic setting properties of a commercially available resin-modified glass ionomer cement were investigated with respect to setting time, mechanical strength, and setting mechanism. It was found to be clinically acceptable whether the setting time was extended or shortened depending on the type of bioactive glass added. The compressive strength of the set cement containing the bioactive glass decreased and was much higher when compared with the conventional type glass ionomer cement containing bioactive glass. The Fourier-transform infrared and 13C CP/MAS-NMR spectroscopies revealed that the extent of the acid-base reaction was larger in the cements containing bioactive glass than in the commercial resin-modified glass ionomer cement because of its high basicity in the bioactive glass. The 27Al MAS-NMR showed that crosslinking of the carboxylates in the polymeric acid by Al proceeded less in the cement containing the bioactive glass.     

Identification of p46 Shc expressed in the nuclei of hepatocytes with high proliferating activity: Study of regenerating rat liver

The adaptor molecule Shc is a proto-oncogene product, and it is known to be associated with cell proliferation. However, the role of Shc in the proliferation and regeneration of hepatocytes remains unknown. In the present study, we report that p46 Shc is specifically expressed in the nuclei of proliferative (or regenerative) hepatocytes, suggesting that p46 Shc protein plays a role in hepatocellular proliferation. The expression of Shc was analyzed in liver tissue after partial hepatectomy (PH) or sham operation in Wistar rats by using immunohistochemistry and/or Western blot analysis. In addition, the expression of various cell cycle-related proteins, such as Cdk4, cyclin D1, PCNA, and Cdk1 was analyzed in the tissues of regenerating rat liver. Furthermore, the tyrosine phosphorylation of Shc was studied in liver tissue after PH or sham operation by immunoprecipitation using a monoclonal phosphotyrosine antibody. Although the protein levels of p52 Shc were unchanged in liver tissues after PH or sham operation, tyrosine phosphorylation was detected only in the regenerating rat liver after PH. The levels of p46 Shc protein were markedly increased in liver tissues during the liver regenerative process. In contrast, p66 Shc was not detected in the liver tissues after PH or sham operation. Western blotting and immunohistochemistry showed that the main location of p46 Shc was in the nuclei of proliferating hepatocytes after PH. These data suggest that p46 Shc expressed in hepatocellular nuclei may be closely related to the proliferation of hepatocytes. Therefore, it is suggested that p46 Shc expressed in hepatocellular nuclei may be a useful marker for detecting hepatocytes with high proliferative activity.     

Characterization of DNA sequences constituting the terminal heterochromatin of the chicken Z chromosome

Two clones, pCZTH5-8 and pCZTH12-8, were isolated from a female chicken genomic library by screening with sequences obtained from genomic libraries which had been constructed from a terminal region of a single Z chromosome of chicken utilizing laser microbeam irradiation and PCR amplification. Fluorescencein situ hybridization to the mitotic Z chromosome and the lampbrush ZW bivalent of chicken demonstrated that both the cloned sequences are located in the heterochromatic region of the Z chromosome at the end opposite to the pairing region with the W chromosome. The sequences pCZTH5-8 and pCZTH12-8 are distributed widely on both the telomeric bow-like loops (TBL) and the region I (short loops region) of the Z lampbrush chromosome. These clones, pCZTH12-8 particularly notably, hybridized also to the TBLs of lampbrush bivalents 1–4 of chicken. Both sequence are transcribed in the lampbrush stage oocytes on the Z chromosome and on other macrobivalents. The subfragment of pCZTH5-8 which hybridizes to the TBLs and the insert of pCZTH12-8 contain regions that are closely similar in sequence. The pCZTH5-8 sequence has no internal repeats and may be part of the 24-kb macrosatellite repeating unit that is evident afterNhel digestion of the genomic DNA. A cloned 24-kb unit, pFN-1, does not show significant DNA curvature, but cytosines of its CpG dinucleotides may be highly methylatedin vivo. This contrasts with the repeat sequences of the W heterochromatin which not only have highly methylated CpG but are also strongly curved. The 24-kb unit is repeated about 830 times in the diploid genome of a female chicken, suggesting that nearly the entire terminal heterochromatin on the Z chromosome consists of this macrosatellite family. Sequences of the greater part of the pCZTH5-8 are restricted to the genusGallus but the sequence of one subregion which hybridizes to TBLs is present in the genomes of the order Galliformes.accepted for publication by M. Schmid     

Effects of pentagastrin and carbachol on the gastric histamine level in α-fluoromethylhistidine-treated mice and rats

Summary The gastric mucosal histamine level in mice increased by about 80% and 100% after fasting for 24 and 48 h, respectively. In non-fasted mice, -fluoromethylhistidine (-FMH), a specific histidine decarboxylase inhibitor, significantly decreased the histamine level, the reduction amounting to 35% and 49%, 2 h and 4 h after treatment, respectively. In mice fasted for 24 h, a significant decrease of 42% was observed 4 h after treatment. However, in mice fasted for 48 h, no significant decrease was seen even 4 h after -FMH treatment. Therefore, the histamine-releasing effect of re-feeding and drugs on the gastric mucosa was examined in vivo, using animals fasted for 48 h and subsequently treated with -FMH. Food given simultaneously with -FMH to 48-h fasted mice significantly decreased the histamine level 4 h later. Pentagastrin and carbachol administered alone (0.25–2.0 mg/kg, i.p.) had no significant effect on the histamine level. However, the combined treatment with these drugs significantly decreased the histamine level. In rats fasted for 48 h and treated with -FMH, pentagastrin (0.25 and 0.5 mg/kg, i.p.) but not carbachol (0.125 – 0.5 mg/kg, i. p.) caused a significant decrease in the mucosal histamine level. In contrast to mice, the effect of the combined treatment with pentagastrin and carbachol was not synergistic in rats. These findings suggest that gastrin acts synergistically with acetylcholine in the histamine release from the gastric mucosa in mice, whereas such synergism may not occur in rats. Send offprint requests to K. Saeki     

Prevention of postischemic reperfusion injury: The improvement of myocardial tissue blood flow after ischemia by terminal Nicorandil-Mg cardioplegia

We evaluated the preventive effect of postischemic reperfusion injury by Nicorandil-Mg cardioplegia given just prior to reperfusion as terminal cardioplegia. Twenty seven dogs were placed on cardiopulmonary bypass and the aorta was cross-clamped for 90 min under hypothermic (17–19°C) cardioplegic arrest. The canine hearts were divided into three groups: in group A (n=10) the hearts were reperfused without any treatment; in group B (n=9) the hearts received coronary perfusion with Nicorandil-Mg solution (Nic, 8 mg/l; Mg, 20 mEq/l; glucose, 50 g/l) for 2 min just prior to reperfusion; and in group C (n=8) the hearts received coronary perfusion with Nicorandil-Mg free solution (glucose, 50g/l). During and after ischemia, the myocardial tissue PCO₂ (t-PCO₂) was continuously monitored by an ion-sensitive field effective transistor (ISFET) sensor. In addition, the myocardial tissue blood flow (TBF), oxygen consumption, and lactate flux were then calculated at 5, 10, 20, and 40 min of reperfusion. In the initial reperfusion period, Group B showed an improved TBF compared to group A and C (at 5 min, group B was 42.7±11.9; group A was 29.4±11.2, P<0.025; and group C was 33.9±9.2% of the preischemic control level, P<0.05). T-PCO₂ in group B was significantly decreased at 5 min of reperfusion (group B, 127.5±22.5 42.5±9.7; group A, 117.5±23.0 85.2±17.4, P<0.001; group C, 122.3 mmHg 68.2±18.7 mmHg, P<0.01), and group B had a better metabolic recovery. These results suggest that terminal Nicorandil-Mg cardioplegia might reduce the rate of postischemic reperfusion injury.     

Identification of risk factors on secondary hyperparathyroidism undergoing long-term haemodialysis with vitamin D3

In order to evaluate the clinical outcome as well as the effectof vitamin D3 treatment on secondary hyperparathyroidism (SHPT)in the patients undergoing long-term dialysis therapy, we conducteda long-term follow-up survey on the demographic characteristicsof 425 patients who were observed for more than 3 years. Allpatients were treated with daily 1(OH)D3 treatment after theinitiation of dialysis. Among them the percentage of patientsneeding parathyroidectomy was 4.9% aggravation of SHPT, 11.8%an increase of the parathyroid hormone (PTH) level without radiographicalabnormalities, 17.4% stable, 56.2% and a decrease of the PTHlevel, 9.7% at the final observation. The average PTH levelsincreased year by year irrespective of the difference of originalrenal disease. Gender, age at the start of dialysis, originalrenal disease, duration of dialysis treatment, the decade ofstarting dialysis, the degree of phosphate control, and thePTH level at starting dialysis were analysed as potential riskfactors for SHPT, and assessed by multivariate analysis. Multivariateanalysis revealed that only the terms of duration of dialysisand the PTH level at starting dialysis were the significantrisks for developing overt SHPT. Logistic regression analysisrevealed that the relative risk was significantly higher inthe patients with more than 10 years history of dialysis andin those with the carboxyterminal PTH levels at the start ofdialysis being more than 5 ng/ml. These results suggest thatthe treatment with daily low-dose vitamin D3 administrationafter dialysis initiation is imperfect; therefore some prophylactictherapy from the predialysis stage is necessary to prevent overtSHPT, which will occur after long-term haemodialysis.     

Therapeutic effect of a CDDP-epirubicin-Lipiodol emulsion on advanced hepatocellular carcinoma

Prior injection of an anticancer agent and Lipiodol mixture is a key point for the treatment of hepatocellular carcinoma (HCC). We therefore prepared a new, improved emulsion of Lipiodol containing a high dose ofcis-diamminedichloroplatinum (CDDP) and epirubicin by replacing the ionic contrast medium (Urografin 67) with a nonionic contrast medium (Iopamidol; Iopamiron 300) and adding phosphatidyl choline. This CDDP-epirubicin-Lipiodol emulsion (CELE) was examined pharmacologically and chemically with the following results. The size of these particles is less than 10 m (diameter) for up to 24 h; the release of 28%–34% of the CDDP and 80%–90% of the epirubicin was estimated in the dissolution test, and 85% of the CDDP and 35% of the epirubicin was retained in the organs in the moment calculation. CELE was injected into 58 HCC patients via a celiac angiographic catheter. In 36 of these patients, the CELE injection was followed by transcatheter arterial embolization (TAE) therapy. Following the administration of CELE as one-shot injection therapy for stage IV HCC, the 1-year survival rate was 59% and the 2-year survival rate was 27%. Moreover, in patients (stage II, 12; stage III, 8; stage IV, 16) who received CELE and subsequently underwent TAE therapy, the 1-year survival rate was 90% and the 2-year survival rate was 67%. The nonionic contrast medium with Lipiodol forms finer emulsified particles, and these particles are more capable of penetrating into the tumor. In addition, the greater pharmacological stability of these particles provides a slow-release effect and prolonged stability of their shape. Finally, theoretically, the use of two major anticancer agents such as CDDP and epirubicin showed a greater clinical effect in the treatment of HCC than either our earlier suspension or a single anticancer agent.Work presented at the Third International Symposium on Treatment of Liver Cancer, Seoul, Korea, 12–13 February 1993     

Serum C-reactive protein level and the impact of cytoreductive surgery in patients with metastatic renal cell carcinoma

PURPOSE: The prognosis of metastatic renal cell carcinoma is extremely poor. In this type of metastatic tumor cytoreductive surgery of the primary tumor is often performed to confirm the histological type or improve the response to immunotherapy with agents such as interferon or interleukin-2. However, the timing and impact of cytoreductive surgery on the success of immunotherapy require further study. We determined the type of metastatic renal cell carcinoma for which cytoreductive surgery is beneficial. MATERIALS AND METHODS: We retrospectively reviewed the records of 58 patients in whom metastatic renal cell carcinoma was diagnosed at our hospital between 1986 and 1997. Three patients were excluded from study because they were judged to be poor candidates for surgery due to poor performance status. Of the remaining 55 patients 34 consented to cytoreductive surgery of the primary tumor and 21 did not. All except 1 patient were treated with interferon therapy. We evaluated the association of pretreatment serum C-reactive protein and the effect of surgery. RESULTS: We noted no significant difference in age at diagnosis, pretreatment serum immunosuppressive acidic protein, site of metastasis or performance status in 34 patients who underwent cytoreductive surgery and 21 who did not. Of the 21 patients in whom pretreatment serum C-reactive protein was within normal limits (less than 1.0 ng./ml.) no significant difference in disease specific survival was observed in those who did and did not undergo surgery (p = 0.4133). On the other hand, of 34 patients in whom pretreatment serum C-reactive protein was elevated (1.0 ng./ml. or greater) the prognosis was significantly better in those who did versus those who did not undergo surgery (p = 0.0054). Particularly the prognosis in patients in whom postoperative nadir C-reactive protein decreased to within normal limits was markedly better than in those in whom it remained elevated (p = 0.0025). CONCLUSIONS: Our study suggests that cytoreductive surgery is beneficial to patients in whom pretreatment serum C-reactive protein is elevated. Particularly, those in whom serum C-reactive protein decreases to within normal limits may expect longer survival when surgery is combined with postoperative immunotherapy. Currently to our knowledge the prognostic factor that predicts postoperative nadir C-reactive protein has not been identified, indicating that cytoreductive surgery of the primary tumor should be performed in patients with elevated pretreatment C-reactive protein and as performance status permits.     

Total Esophagectomy versus Proximal Esophagectomy for Esophageal Cancer at the Cervicothoracic Junction

To investigate the adequate extent of esophagectomy and lymphadenectomy for an esophageal cancer localized at the cervicothoracic junction, the mortality and morbidity rates, survival rates, and patterns of recurrence were retrospectively analyzed in two groups—14 patients who underwent total esophagectomy with or without laryngectomy and 15 patients who underwent proximal esophagectomy with or without laryngectomy—at Kurume University Hospital from 1981 to 1996. Proximal esophagectomy with or without laryngectomy resulted in a lower hospital mortality rate and better overall survival for patients who underwent curative esophagectomy compared with total esophagectomy with or without laryngectomy. Multivariate analysis indicated that the extent of esophagectomy (total esophagectomy versus proximal esophagectomy) was not a prognostic factor. The incidence of recurrence was not different between the two groups. Lymph node metastasis or recurrence from such esophageal cancers was localized to the neck and upper mediastinum. For an esophageal cancer localized at the cervicothoracic junction, therefore, proximal esophagectomy with or without laryngectomy and with cervical and upper mediastinal lymphadenectomy could be better indicated for preselected patients.