Instability of reference diameter in the evaluation of stenosis after coronary angioplasty: Percent diameter stenosis overestimates dilative effects due to reference diameter reduction

Purpose: To examine changes in the reference segment luminal diameter after coronary angioplasty. Methods: Sixty-one patients with stable angina pectoris or old myocardial infarction were examined. Coronary angiograms were recorded before coronary angioplasty (pre-angioplasty) and immediately after (post-angioplasty), as well as 3 months after. Artery diameters were measured on cine-film using quantitative coronary angiographic analysis. Results: The diameters of the proximal segment not involved in the balloon inflation and segments in the other artery did not change significantly after angioplasty, but the reference segment diameter significantly decreased (4.7%). More than 10% luminal reduction was observed in seven patients (11%) and more than 5% reduction was observed in 25 patients (41%). More than 5% underestimation of the stenosis was observed in 22 patients (36%) when the post-angioplasty reference diameter was used as the reference diameter, compared with when the pre-angioplasty measurement was used and more than 10% underestimation was observed in five patients (8%). Conclusion: This study indicated that evaluation by percent diameter stenosis, with the reference diameter from immediately after angioplasty, overestimates the dilative effects of coronary angioplasty, and that it is thus better to evaluate the efficacy of angioplasty using the absolute diameter in addition to percent luminal stenosis.     

Protein phosphatase 2Aα involvement in granulocytic differentiation of HL-60 cells

Protein phosphatase 2Aα (PP-2Aα) is one of the catalytic subunits of PP-2A, which is composed of catalytic and regulatory subunits. In fission yeasts, PP-2A mutants cause mitotic defects and strikingly different cell cycle phenotypes. In rat hepatocellular carcinomas, mRNA expression of PP-2Aα was increased compared to that of normal hepatocytes. From these studies, PP-2Aα has been thought to be involved in proliferation, and we expected that PP-2Aα would decrease in HL-60 cells on dimethyl sulfoxide(DMSO)-induced granulocytic differentiation with decreased growth rate. In this study, we show that PP-2Aα expression increases in HL-60 cells on DMSO-induced granulocytic differentiation, while PP-1γ, which is one of catalytic subunits of protein phosphatase 1, expression did not change significantly. These results suggest that PP-2Aα may be involved in regulation of differentiation of hematopoietic cells.     

Etiologic and Pathogenetic Study of Mental Retardation with Multiple Congenital Anomalies

Etiology and pathogenesis of MCA/MR in 1,023 patients (618 male; 405 female) with mental retardation were studied. Of 1,023 patients, there were 563 cases (317 male; 246 female) with MCA (55%). Among the MCA patients, there were 303 (156 male; 147 female) whose primary etiology was clarified (53.8%). Among the 260 patients with MCA/MR of unknown etiology, there were 23 with recognizable syndromes of unknown etiology and 7 previously reported by us as possibly having a new malformation syndrome. We had 569 patients with mental retardation of unknown etiology including 236 (41.5%) who were involved with MCA.     

Bi-weekly chemotherapy with medium-dose docetaxel for advanced and recurrent breast cancers (The 15th study of Keiji Breast Cancer Study Group)

The efficacy and safety of bi-weekly administration of medium-dose docetaxel (TXT) were evaluated in patients with advanced and recurrent breast cancers. The additional effect of 5'-DFUR for non-responders was also evaluated. Forty patients with advanced and recurrent breast cancers were treated and 38 cases of 40 were evaluated (34 with recurrent cases and 4 with advanced cases). All cases were female, and their mean age was 56.0 (38-74). TXT of 60 mg/body, which was equivalent to 30-50 mg/m2 for standard-sized Japanese women, was administered every two weeks. 5'-DFUR of 800 mg/body was added for non-responders after 5 weeks. The response rate was calculated from the data of 32 cases with measurable lesions, and side effects were evaluated in about 34 cases with exact records. Two hundred seventy-one courses were performed for 38 patients (4-24 courses per person, average 7.13 courses). The mean dosage per course of TXT was 58.4 mg/body (38.3 mg/ m2). Three complete and 7 partial responses were observed (overall response rate: 31.3%). Ten non-responders were evaluated for the additional effect of 5' DFUR, and one case reached PR. Grade 3/4 bone marrow suppression occurred in 9 patients, and Grade 3/4 general malaise was observed in two patient. According to the results, bi-weekly administration of medium dose TXT is an active and safe regimen in patients with advanced and recurrent breast cancers. The additional effect of 5'-DFUR was observed in one of 10 non-responders of bi-weekly chemotherapy with medium-dose TXT.     

Cerebral concentrations of myo-inositol in rats with induced brain death

In anaesthetized, mechanically ventilated rats with brain death induced by epidural balloon inflation, we assessed the levels of cerebral myo-inositol in three brain areas 4 h after brain death had been confirmed. The levels were measured using HPLC, along with the water content. Myo-inositol levels were significantly increased in the cerebellum (P<0.05) and decreased in the brainstem (P<0.001), compared to findings in controls. Such changes can serve as hallmarks of brain death.     

Glucocorticoid hormone regulates the circadian coordination of micro-opioid receptor expression in mouse brainstem

The 24-h variation in glucocorticoid secretion from the adrenal cortex is observed not only in nocturnally active rodents but also in diurnally active humans. Although the cyclic change in circulating glucocorticoid levels is thought to influence the efficacy and/or toxicity of many drugs, the mechanism underlying the influence remains poorly understood. In this study, we demonstrate that the 24-h variation in circulating glucocorticoid levels modulates the analgesic effect of morphine by regulating the expression of the mu-opioid receptor. Significant time-dependent variations in the mRNA levels of the mu-opioid receptor and its binding capacity were observed in mouse brainstem. The analgesic effect of morphine was enhanced by administering the drug when mu-opioid receptor levels were increased. However, corticotrophin-releasing hormone (CRH)-deficient mice, disrupting the 24-h rhythm of glucocorticoid secretion, showed no significant time-dependent variation in the expression of the mu-opioid receptor. As a consequence, there was no significant dosing time-dependent difference in the analgesic effect of morphine in CRH-deficient mice. A single administration of corticosterone significantly induced the expression of the mu-opioid receptor in the CRH-deficient mouse brainstem and also enhanced the analgesic effect of morphine. These findings suggest a mechanism underlying the time-dependent variation in mu-opioid receptor function and provide clues to select the most appropriate time of day for administration of morphine.     

Induction of hepatocellular carcinoma in rat liver by initial treatment with benzo(a)pyrene after partial hepatectomy and promotion by phenobarbital

The hepatocarcinogenicity of benzo(a)pyrene(BP) in the rat was examined. Rats were treated with BP after partial hepatectomy and then kept on a diet containing phenobarbital (PB) as a promoter. Tumors including a hepatocellular carcinoma developed in the rat liver by week 52.     

Expression and possible role of neuronal calcium sensor-1 in the cerebellum

Neuronal calcium sensor-1 (NCS-1) is a member of EF-hand calcium-binding protein superfamily, which is considered to modulate synaptic transmission and plasticity. In this mini-review, we first summarize distribution of NCS-1 in the cerebellum. NCS-1 is mainly detected in postsynaptic sites, such as somata and dendrites of Purkinje cells, stellate/basket cells and granule cells. In addition, GABAergic inhibitory stellate/basket cell axon terminals also contain NCS-1. Secondly, we describe cerebellar compartmentation defined by NCS-1. The NCS-1 immunostaining displayed characteristic parasagittal-banding pattern in the Purkinje cell layer and molecular layer, whereas there were no apparent bands in the granule cell layer. The alternating positively and negatively NCS-1-labeled Purkinje cell clusters contributed to this cerebellar compartmentation. In contrast, stellate/basket cells were uniformly NCS-1-positive throughout the cerebellum. Interestingly, NCS-1 and zebrin II exhibited a similar parasagittal-banding pattern. But it is noteworthy that NCS-1-negative/zebrin II-positive Purkinje cell clusters were detected selectively in anterior lobule vermis and paraflocculus. These results suggest that NCS-1 defines a novel pattern of cerebellar cortical compartmentation. Lastly, we describe recent data suggesting some relationship between NCS-1 and cerebellar long-term depression-related molecules, and discuss the possible role of NCS-1 in the cerebellum.