Extracellular adenosine 5'-ATP-induced calcium signaling in isolated vestibular ganglion cells of the guinea pig

Extracellular adenosine 5'-triphosphate (ATP)-induced intracellular calcium concentration ([Ca2+]i) changes in acutely isolated vestibular ganglion cells (VGCs) of the guinea pig were investigated using the Ca2+ -sensitive dye Fura-2. Extracellular ATP induced an increase in [Ca2+]i in VGCs in a dose-dependent manner. ATP induced an increase in [Ca2+]i even in the absence of extracellular Ca2+ (1 mM Ethylene Glycol-bis (beta-aminoethyl Ether) N,N,N',N'-Tetraacetic Acid (EGTA)), thus suggesting that ATP induces Ca2+ release from the intracellular stores. The P2-receptor antagonists suramin and reactive blue 2 inhibited the ATP-induced [Ca2+]i increase in a dose-dependent manner. The P1-receptor agonist adenosine did not induce any changes in [Ca2+]i. These results suggest that VGCs may possess a P2-purinergic receptor but not a P1-purinergic receptor. La3+, a receptor-mediated calcium channel blocker, inhibited the ATP-induced [Ca2+]i increase but, in contrast, nifedipine, a L-type calcium channel blocker, did not. These results suggest that ATP induces both a Ca2+ -release from the intracellular stores and a Ca2+ influx from the extracellular space through La3+ -sensitive and nifedipine-insensitive Ca2+ channels in VGCs. Our results also suggest that extracellular ATP may act as a neurotransmitter or neuromodulator of the vestibular peripheral system in the guinea pig.     

Developmental expression of myotonic dystrophy protein kinase in brain and its relevance to clinical phenotype

To investigate the pathophysiologic role of myotonic dystrophy protein kinase (DMPK) in the brain in myotonic dystrophy (MD), the developmental characteristics of DMPK immunoreactivity in the central nervous system and its alteration with disease were studied. Eleven patients’ brain with MD (5 congenital form, 6 adult form) were examined by immunohistochemistry using a specific antibody against synthetic DMPK peptides, anti-peptide DM1, and compared with 30 control brains, including 16 age-matched controls. In controls, DM1-immunoreactive neurons appeared in the early fetal frontal cortex and cerebellar granule cell layer, persisting through 29 weeks of gestation and then disappearing. In contrast, immunoreactive neurons continued to persist in the cerebral cortex and cerebellar granule cell layer of MD patients. When we counted DM1-immunoreactive neurons, the increase over controls was greater in the congenital form of MD than in the adult form, and was greater in the cerebrum than in the cerebellum in both forms of MD. DM1 immunostaining was predominantly nuclear, mirroring Western blotting of subcellular fractions. Differences in DM1 expression related to development and to the two forms of MD may be closely related to the pathogenesis of mental retardation in this disease. Received: 30 July 1999 / Revised: 21 January 2000 / Accepted: 1 February 2000     

Molecular and immunological dissection of diffuse large B cell lymphoma: CD5+, and CD5- with CD10+ groups may constitute clinically relevant subtypes.

Diffuse large B cell lymphoma (DLBL) constitutes the greatest percentage of adult non-Hodgkin's lymphomas and represents a diverse spectrum of lymphoid neoplasms. Clinicopathologic, phenotypic and genotypic findings were correlated and compared for 63 DLBL cases to investigate whether they represent clinically relevant subtypes. They were all cyclin D1 negative and were phenotypically divided into three groups, ie group I (CD5+ type, n=11), group II (CD5- CD10+ type, n=19), and group III (CD5- CD10- type, n=33). Data were correlated by observing the respective gene rearrangement and expression of BCL2 and BCL6. In clinical aspects, the group I cases demonstrated a significantly inferior survival than those of the other two groups (log-rank test, P = 0.016). Although rearrangement of BCL2 and BCL6 did not show any inclination to a specific subgroup, the immunohistochemical detection of BCL2 was less frequent, at a statistically significant level (P=0.011), in group II (50%) than in group I (82%) and III (82%) cases. This appears to confirm the unique aspect of the CD5- CD10+ type DLBL, indicating a certain relationship with the normal germinal center cells which usually lack BCL2 expression. The BCL6 protein expression was detected in most of the present DLBL cases (92%) irrespective of this grouping. These data suggest that the phenotypic delineation by the detection of CD5 and CD10 will improve our understanding of DLBL and be helpful in a future subgrouping of DLBL.     

Angiotensin II in human veins: development of rapid desensitization and effect of indomethacin

1. The present study investigated whether rapid desensitization (tachyphylaxis) develops after exposure of human hand veins to angiotensin (Ang)II and whether pretreatment with indomethacin affects its development. 2. Venoconstrictor responses to increasing (2-256 ng/min) and constant (50 ng/min) doses of AngII and noradrenaline (NA) infusion were obtained in six healthy male subjects using the dorsal hand vein technique. After pretreatment with indomethacin and placebo, venoconstrictor responses to 50 ng/min AngII infusion were obtained in eight healthy male subjects. 3. The maximal mean (+/- SD) venoconstrictor response to NA (obtained with 256 ng/min NA) was 93.1 +/- 4.7%, whereas that to AngII (obtained with doses between 16 and 128 ng/min) was 43.8 +/- 12.2%. Continuous infusion of NA induced constant venoconstriction, whereas the venoconstrictor response to AngII peaked 3 min after the beginning of infusion and, thereafter, was attenuated. 4. Venoconstriction in response to constant AngII infusion after indomethacin pretreatment was significantly larger than that after placebo from 6 to 18 min after the initiation of infusion. 5. These findings show that rapid desensitization to AngII develops in human hand veins and this is compatible with the hypothesis that vasodilator prostaglandins are involved in the development of this desensitization.     

A long-survival case of gastric cancer with multiple liver metastasis: usefulness of intraoperative multimodality therapy and post-operative intra-arterial chemotherapy for liver lesions

A 62-year-old man was found to have advanced cancer of the gastric cardia with multiple liver metastasis. Total gastrectomy was performed, and 11 hepatic lesions were simultaneously treated by intraoperative multimodality therapy. The therapy included hepatic resections for seven easily-resectable lesions, microwave coagulation therapy for two lesions, and ethanol injection therapy for two. Post-operative intra-arterial infusion of 1,000 mg of 5-FU was performed weekly or every two weeks through the hepatic artery using a reservoir. No recurrence was found during the follow-up period of 35 months. When local control is obtained during surgery in patients with gastric cancer with multiple liver metastasis, intraoperative multimodality therapy and post-operative intra-arterial chemotherapy should be performed for liver lesions.     

Actual situations and problems of patients receiving home IVH--trial use of an assessment chart for outpatients

In order to improve the quality of life (QOL) and continue nursing, we used an assessment chart to investigate the actual situations and problems of the patients receiving home intravenous hyperalimentation (IVH). From January, 1997 to June, 1999, we investigated 20 patients with home IVH. To 7 patients among them, we asked questions using Kurihara's assessment chart for QOL, plus our original questions concerning IVH. The mean age of the patients was 61 years old, and 19 of them had advanced cancers. Forty percent of the patients maintained the IVH all by themselves and 10% of the patients needed the support of their family. The remaining 50% of the patients left all to their family. There were 9 incidents of trouble during the maintenance of the IVH. Almost all patients from whom informed consent had been received were satisfied with the home IVH. On the contrary, all patients who had not given informed consent were not satisfied with the home IVH. According to the results of the assessment chart, even if the total points were low, the points for the IVH were high in the patients had given informed consent. The main reason for lower QOL was pain. The points for the families were lower than those for the patients. They sometimes complained of uneasiness and dissatisfaction with the support they received. We conclude that therapies to improve symptoms and mental state are necessary to satisfy the patients, and that it is important to support not only the patients but also their families.