Highly enantioselective hydrogenation of alpha-dehydroamino acids by rhodium complexes with new unsymmetric P-chirogenic bisphosphine ligands.

[figure: see text] New rhodium catalysts with unsymmetric P-chirogenic bis(phosphino)ethanes, BisP*-Rh, exhibited very high enantioselectivity (98-99%) in the hydrogenation of alpha-dehydroamino acid derivatives. Such high enantioselectivity should result from the asymmetric environment around the Rh atom, as was shown in the molecular structure of the catalyst analyzed by X-rays. The asymmetry can be controlled by the combination of the alkyl groups on the two phosphorus atoms.

Constitution of Grignard reagent RMgCl in tetrahydrofuran.

The constitution of Grignard reagent, RMgCl (R = Me, tBu, Ph or benzyl), was investigated in the solid state by means of X-ray crystallography and in THF by coldspray ionization mass spectrometry (CSI-MS). Three types of crystal structures, (a) [Mg2(mu-Cl3)(THF)6](+)*[RMgCl2(THF)](-), (b) R2Mg4Cl6(THF)6, and (c) [2Mg2(mu-Cl3)(THF)6](+)*[R4Mg2Cl2]2-, were identified, and MeMg2(mu-Cl3)(THF)4-6 were detected as major species of MeMgCl in solution.

Stereospecific reduction of phosphine oxides to phosphines by the use of a methylation reagent and lithium aluminum hydride.

[figure: see text] Various phosphine oxides are efficiently reduced by the use of a methylation reagent and lithium aluminum hydride. Optically active P-chirogenic phosphine oxides are also reduced with inversion of configuration at phosphorus atom by treatment with methyl triflate, followed by reaction with LiAlH4.

Highly enantioselective hydrogenation of (E)-beta-(acylamino)acrylates catalyzed by Rh(i)-complexes of electron-rich P-chirogenic diphosphines.

Excellent enantioselectivities up to 99.7% were achieved in the hydrogenation of (E)-beta-(acylamino)acrylates by the use of Rh(I)-complexes of electron-rich diphosphines, t-Bu-BisP and t-Bu-MiniPHOS. Low-temperature NMR experiments testify that monohydrides with beta-carbon atom of the substrate bound to rhodium are involved in the catalytic cycle.

Beneficial effects of TDN-345, a novel Ca2+ antagonist, on ischemic brain injury and cerebral glucose metabolism in experimental animal models with cerebrovascular lesions.

The effects of TDN-345 on mortality and ischemic neurological deficit following transient global cerebral ischemia in Mongolian gerbils and also the rate of local cerebral glucose utilization (LCGU) in stroke-prone spontaneously hypertensive rats (SHRSP) with cerebrovascular lesions were investigated. In Mongolian gerbils, ischemia was produced by clamping the bilateral common carotid arteries for 15 min. TDN-345 (0.1-1.0 mg/kg) dose-dependently decreased the mortality and ischemic neurological deficit score when administered orally twice, 60 min before ischemia and 90 min after recirculation. Additionally, TDN-345 (0.2 or 1.0 mg/kg, p.o. once daily for 3 weeks after the onset of stroke) decreased the mortality and recurrence of stroke in SHRSP. To determine the site of action of TDN-345 in the brain, the rate of LCGU in various brain regions in SHRSP with stroke was examined using a [14C]2-deoxy-D-glucose method. The rate of LCGU decreased significantly in all the brain regions in SHRSP with stroke compared with Wistar-Kyoto (WKY) control rats, whereas the reduction in the rate of LCGU in SHRSP with stroke was prevented by TDN-345 treatment, especially in the sensorimotor cortex and locus coeruleus. These results suggest that TDN-345 has therapeutic efficacy in the treatment of cerebrovascular disease.

Clinical significance of pulmonary metastases in stage D2 prostate cancer patients.

Several prognostic factors such as the extent of bone metastases (EOD) in advanced prostate cancer (PCa) have been reported. Metastasis of the lung is rarely a significant clinical factor in the management of prostate cancer. The present study evaluates the clinical significance of lung metastases. We retrospectively reviewed the PCa database to identify patients with pulmonary metastases at initial diagnosis. The medical records of the patients were examined with respect to age, histologic grade, EOD score, marker response to endocrine therapy and clinical outcome. We then compared several potential clinical factors between patients with and without pulmonary metastases. Next, we retrospectively reviewed autopsy records of 60 Japanese patients who died of hormone-refractory metastatic PCa with particular focus upon metastatic profiles. A comparative study of stage D(2) patients with (n=20) and without (n=77) pulmonary metastases found no significant differences in EOD score, performance status, marker response and survival. Only tumor grade was better in the group with, than without pulmonary metastases (P=0.0120, chi-square analysis). In the series of autopsies, we found pulmonary metastases in 38 cases (63%), following metastases of the bone (57 cases, 95%) and lymph nodes (52 cases, 87%). A retrospective analysis of survival showed that patients with bone or lymph node metastases had a positive relative risk. In contrast, lung metastasis could be a positive prognostic indicator, although the findings were not statistically significant. These data suggest that the presence of pulmonary metastasis has no ominous impact on clinical course and disease outcome even in patients with disseminated prostate cancer.

Laparoscopic adrenalectomy for pheochromocytoma.

We reviewed 10 cases of laparoscopic adrenalectomy for pheochromocytoma and compared the results with those of a recent series of 11 patients who underwent open adrenalectomy. Of the 10 cases, the tumor was removed successfully in all cases except in one case with laparoscopy that required open laparotomy. A pair of laparoscopic coagulating scissors was utilized in all except the initial two cases. In the laparoscopy group (excluding the initial two cases and the case that required conversion to open surgery), mean operative time and blood loss were 145 min and 55 ml, respectively. No significant difference was observed in mean operative time between the laparoscopy group and the open surgery group (165 min for open surgery). Mean blood loss of the laparoscopy group was significantly less than that of the open surgery group (330 ml for open surgery, P = 0.01). Mean intervals to first ambulation and oral intake, and postoperative hospital stay of the laparoscopy group, tended to be less than those of the open surgery group, although no statistical significance was observed (2.3 versus 3.2 d, 2.9 versus 3.6 d, and 12 versus 14 d, respectively). We conclude that laparoscopic adrenalectomy for pheochromocytoma is equally effective and less invasive than open adrenalectomy and should be considered the therapy of choice even for pheochromocytoma.

Case report of malignant splenic tumor.

Primary angiosarcoma and malignant lymphoma of the spleen are uncommon. We report such tumors in a 44-year-old-woman and a 51-year-old-man. The value of diagnostic imaging by US and CT is emphasized. These techniques can establish the solid nature of the mass and may be the first methods to suggest malignancy.

[Heparin affinity high-performance liquid chromatography as an alternative to bioassay of CS23 mutein of recombinant human basic fibroblast growth factor].

We investigated whether a chemical assay by high-performance liquid chromatography (HPLC) as an alternative to the complicated and time-consuming bioassay for CS23 mutein of recombinant human basic fibroblast growth factor (rhbFGF-CS23) using the fetal bovine heart endothelial cell line ATCC CRL 1395. Physically, chemically or enzymatically denatured rhbFGF-CS23 was subjected to heparin affinity (HA)-HPLC and the bioassay. Good agreement was observed between the results obtained by these two methods. Moreover, HA-HPLC gave much more reproducible results (RSD = 1.9%, n = 6) than the bioassay (RSD = 7.4%, n = 18). HA-HPLC is therefore a simple, accurate and reproducible alternative to the bioassay for quality control and stability studies for rhbFGF-CS23 preparations. HA-HPLC is also considered to be applicable to assays for FGFs which have heparin affinity and biological activity similar to those of the CS23 mutein.

[Technetium-99m-pyrophosphate myocardial scintigraphy in polymyositis--a case report].

A patient with polymyositis who had cardiac involvement underwent myocardial scan with technetium-99m-pyrophosphate. We used Activity Index for evaluating myocardial uptake of technetium-99m-pyrophosphate, which correlated with the degree of serum creatine phosphokinase elevation. Our findings indicate that these examinations may be helpful for identifying patients who have cardiac involvement and evaluating their response to the treatment with corticosteroids or immunosuppressants.

[Intra-arterial chemotherapy for invasive bladder cancer].

Between July 1993 and May 1999, 36 patients with invasive bladder cancer were treated with intra-arterial chemotherapy using cisplatin and pirarubicin, and their treatment outcome was evaluated. Clinical CR was obtained in 18 patients, PR in 13, and NC in 5, for an overall response rate of 86%. The median follow-up for evaluating patients was 24 months (2-70 months). The bladder was preserved in 13 of 18 patients showing CR and in 4 of 13 patients showing PR. The 5-year cause-specific survival rate for the 36 patients was 56%. The grade factor did not effect the survival rate significantly. Compared with stage T2, stage T3 yielded a significantly poor prognosis, especially with grade 3. Intra-arterial chemotherapy was confirmed useful as a regional treatment, but not sufficient as a systemic treatment. Thus the selection of patients for this therapy was considered to require exact staging and assessment of the effectiveness.

[Studies on alteration in biventricular dimensions during stepped elevation in pulmonary arterial pressure with special reference to right ventricular bellows action].

A new method for inserting ultrasonic crystals into the interventricular septum (IVS) of dogs was performed to measure the right and left ventricular septum-to-free wall dimensions (RVD, LVD) in a line. The advantage of this technique is minimal damage of the pericardium and no damage of the ventricular wall. The segmental lengths in the right and left ventricles (RVSL, LVSL) were also measured. Stepped elevation of pulmonary arterial pressure induced by ligation of pulmonary arterial branches caused an increase in RVD and a decrease in LVD. IVS shifted to the left and transseptal pressure gradient was reduced. RVD and RVSL increased and percent shortening in RVD and RVSL during ejection decreased with pulmonary hypertension. Although the change in RVD and RVSL basically related each other, those changes in RVD was more evident than in RVSL. Thus, the measurement of RVD and RVSL is indispensable for investigating the right ventricular function. There was a high correlation between the stroke volume and the shortening in RVD (expressed as percent of the control value, respectively) during ejection in pulmonary hypertension (F = 13.88 greater than F 1(20)(0.005) = 9.94), therefore we speculate that right ventricular bellows action is essential in blood ejection from the right ventricle. Furthermore the stroke volume decreased as the shortening in RVSL during ejection decreased (F = 3.17 greater than F 1(20)(0.1) = 2.97), therefore shortening in RVSL is thought to be an important factor causing bellows action, however further investigation is necessary.

Does presence of prostate cancer affect serum testosterone levels in clinically localized prostate cancer patients?

The relationships between serum level of testosterone (T) and prostate cancer (PCa) are complex. The present study evaluated whether presence of PCa alters serum T levels. Subjects were 125 patients with clinically localized PCa treated using radical prostatectomy (RP), for whom pretreatment T levels were recorded. We investigated clinical and pathological factors such as pretreatment serum T level, age, pretreatment prostate-specific antigen, Gleason score and pathological stage. Serum T and human luteinizing hormone (LH) levels before and after RP were then compared in 118 of the 125 patients. Mean pretreatment T level was significantly higher in patients with organ-confined PCa (pT2; 4.03+/-1.50 ng ml(-1)) than in patients with nonorgan-confined cancer (pT3; 3.42+/-1.06 ng ml(-1); P=0.0438). No association existed between pretreatment serum T level and pathological Gleason score. After RP, serum T level (5.60+/-1.90 ng ml(-1)) was significantly elevated compared to preoperative level (3.89+/-1.43 ng ml(-1); P<0.0001). In parallel, significant increases were seen in postoperative serum LH level (6.86+/-3.64 ng ml(-1)) compared to preoperative level (5.11+/-2.47 ng ml(-1); P=0.0001). In contrast, differences in serum T levels according to pathological stage disappeared postoperatively (P=0.5513). Significant increases in serum T and LH levels were seen after RP, compared to preoperative levels in parallel. This study suggests that serum T levels are altered by the presence of PCa, supporting the possibility that PCa may inhibit serum T levels with negative feedback in the hypothalamic-pituitary axis.