Robust axonal sprouting and synaptogenesis in organotypic slice cultures of rat cerebellum exposed to increased potassium chloride

Organotypic slices of the rat cerebellum, cultured in physiological levels [K+]o (5 mM) for 14 days, loose the majority of granule cells in the anterior lobe resulting in few axons and atypical Purkinje cell dendrites with vacant spines. When the culture medium was switched from 5 mM to 20, 30 or 40 mM [K+]o during the last 7 days of cultures, slices developed axons with numerous vesicle-filled boutons that made synaptic contact with Purkinje cell spines. Most boutons had one or two spine profile contacts, while some were unusually large. Enlarged boutons abutted Purkinje cell somata or their dendrites, causing intervening spines to invaginate terminals to form rosette synaptic complexes. Calbindin immuno-labeling excluded Purkinje cell axonal collaterals as the source of rosette boutons and suggested a granule cell origin. Quantification of vacant spines as compared to those on boutons revealed a threshold for potassium, between 10 and 20 mM, where the number of synaptic spines increased and vacant spines decreased drastically. These findings suggest that elevated [K+]o triggers an activity-dependent plasticity in rat cerebellar slice cultures by promoting axonal sprouting with formation of vesicle-filled boutons and synaptogenesis on open receptor sites of Purkinje cell spines.     

Pulse wave velocity can predict hemodynamic responses to induction of anesthesia and tracheal intubation

BACKGROUND: The degree of aortic stiffness can be evaluated by noninvasive measurement of pulse wave velocity (PWV). We investigated hemodynamic responses to induction of anesthesia and tracheal intubation, and hypothesized that preoperative measurement of PWV might predict these responses. METHODS: PWV was measured before operation by using automatic PWV measurement device. Patients were anesthetized with fentanyl (1 microg x kg(-1)) and propofol (target controlled infusion at 2.5 microg x ml(-1)), and tracheal intubation was facilitated with vecuronium (1.5 mg x kg(-1)). Hemodynamic data were recorded from the start of anesthesia to 5 minutes after the tracheal intubation. RESULTS: Twenty patients completed the study. There was a significant correlation between PWV and percent changes in systolic blood pressure during anesthesia induction. However, a significant correlation between PWV and percent changes in systolic blood pressure after tracheal intubation was found only in the patients without antihypertensive medications. CONCLUSIONS: Preoperative PWV measurement was useful to predict hemodynamic responses to induction of anesthesia and tracheal intubation.     

Radiofrequency ablation combined with transcatheter arterial chemoembolization for hepatocellular carcinoma--CT examination during the follow-up period

Radiofrequency ablation (RFA) combined with transcatheter arterial embolization (TAE) can increase the volume of coagulation necrosis to treat patients with hepatocellular carcinoma. Furthermore, in clinical practice, RFA combined with TAE using iodized oil and gelatin sponge often induced the sub-segmental or segmental necrosis toward the liver periphery of the ablated lesion. In this study, we compared the CT findings and histological characteristics of peripherally spreading necrosis induced by this combination therapy for 12 patients with hepatocellular carcinoma. In all cases, complete necrosis of ablated lesions and peripherally spreading necrotic areas were confirmed by CT examination. The histochemical (lactate-dehydrogenase, maleate-dehydrogenase, and NADPH-diaphorase) stained specimens, biopsies from ablated lesions and peripherally spreading necrotic areas, were absent suggesting a 100% cellular destruction. No incomplete local treatments after the therapy were obtained during the 4-26 months of follow-up periods. We conclude that RFA combined with TAE using iodized oil and gelatin sponge makes it possible to induce the segmental or sub-segmental necrosis including tumors.     

Persistent insomnia is a predictor of hypertension in Japanese male workers

Insomnia is one of the most common complaints at worksites, as well as in the general population. This study aims to assess the effect of insomnia on the development of hypertension in Japanese male workers. Using the annual health examination database of a Japanese telecommunication company, eligible middle-aged male participants in the 1994 health examination were followed up until 1998 or the development of hypertension (either initiation of antihypertensive therapy or a systolic blood pressure > or = 140 mmHg and/or a diastolic blood pressure > or = 90 mmHg). The effect of difficulty initiating sleep (DIS) was assessed with a DIS dataset (n=4,794), which included non-DIS (n=4,602) and persistent-DIS (n=192) subjects. That of difficulty maintaining sleep (DMS) was assessed with a DMS dataset (n=4,443), which included non-DMS (n=4,157) and persistent-DMS (n=286) subjects. The incidence of hypertension among persistent-DIS (40.1%; 130.7 per 1,000 person-yr) was significantly higher than that among non-DIS (30.6%; 89.9 per 1,000 person-yr). The incidence of hypertension among persistent-DMS (42.3%; 136.7 per 1,000 person-yr) was significantly higher than that among non-DMS (30.7%; 90.8 per 1,000 person-yr). After adjusting for potential confounding factors (i.e. age, body mass index, smoking, alcohol drinking, and job stress), persistent complaints of DIS and DMS were significantly associated with an increased risk of hypertension (OR=1.96; 95%CI: 1.42-2.70 and OR=1.88; 95%CI: 1.45-2.45, respectively). Persistent insomnia may be a useful predictor of hypertension in Japanese male workers.     

Telomerase activity in Papanicolaou smear-negative exfoliated cervical cells and its association with lesions and oncogenic human papillomaviruses

OBJECTIVE: The goal of this study was to evaluate telomerase activity in exfoliated cervical cells and its association with cytology, pathology, and human papillomavirus (HPV). METHODS: Telomerase activity and HPV DNA sequences were examined in the exfoliated cervical cells from a general population of 245 women aged more than 30 years undergoing routine cervical screening by Papanicolaou smear. The women who were found to have telomerase activity or abnormal cytology in their exfoliated cervical cells were examined for cervical lesions by colposcopy and biopsy. RESULTS: Cytology for our population (mean, 56 years) revealed only one abnormal smear (1/245, 0.4%), in which a cervical intraepithelial neoplasia grade I (CIN I) lesion was found. The exfoliated cervical cells used to prepare the smear were negative for telomerase and contained low-risk HPV DNA. Telomerase activity was found in 16 exfoliated cell samples (16/245, 6.5%); high-risk HPV DNA was found in 9 of these samples (9/16, 56%) and 9 of the biopsy specimens that could be evaluated from patients testing positive for telomerase revealed CIN I lesions (9/11, 82%). CONCLUSIONS: Telomerase activity is often associated with high-risk HPV infection and it is suggested that telomerase assay can help to detect occult cervical lesions.     

Apoptosis and Ki-67 expression in adenomyotic lesions and in the corresponding eutopic endometrium.

OBJECTIVE: To examine biologic and proliferative properties of adenomyotic lesions and to determine whether adenomyotic lesions originate in the basal layer of the eutopic endometrium. METHODS: We examined eutopic and ectopic endometria from 23 patients with adenomyosis. To obtain evidence for the induction of programmed cell death, apoptotic cells were identified using a modified terminal deoxynucleotidyltransferase-biotin nick end-labeling method. To evaluate cell death repressor activity, bcl-2 gene expression was examined using immunohistochemical staining. As a proliferative marker, Ki-67 expression was also examined immunohistochemically. RESULTS: In the eutopic endometrium, apoptosis was most frequently observed in epithelial cells during mid- to late secretory phases, although it was rarely found during early proliferative through early secretory phases (P<.01). In contrast, bcl-2 gene expression inversely correlated with the appearance of apoptosis. A similar tendency was observed in stromal cells. In the ectopic endometrium of adenomyosis, endometrial dating revealed that secretory change was rare, even in the secretory phase, and that induction of apoptotic cells as well as bcl-2 gene expression showed no cyclic change. In stromal cells of the ectopic endometrium, apoptosis was more frequent than was seen in the eutopic endometrium, in all menstrual phases (P<.05). Ki-67 was constantly expressed in the glandular epithelium of the ectopic endometrium, irrespective of the menstrual phases, whereas in the secretory phase it was less expressed in the eutopic endometrium of functional and basal layers (P<.01). CONCLUSION: The induction of apoptosis seems to be regulated by hormonal changes in the eutopic endometrium and has an inverse correlation with bcl-2 gene expression. The ectopic endometrium in adenomyosis is rarely influenced by hormonal change and has different biologic and proliferative properties than events observed in the eutopic endometrium findings, which strongly suggest that the adenomyotic lesion does not originate in the basal endometrium.     

Effect of mono- and diaminopyridines on release of [3H]norepinephrine from isolated guinea-pig atrium

Neurochemical evidence has been obtained that 4-aminopyridine, 3,4-diaminopyridine and 3,3-dimethyl-1-(4-amino-3-pyridyl)urea HBr (LF-14), concentration-dependently enhanced the stimulation-evoked release of [3H]norepinephrine ([3H]NE) from isolated guinea-pig atrium. The effects of aminopyridines, compounds known to inhibit potassium channels, were Ca0-dependent. High pressure liquid chromatography, combined with radiochemical detection, indicated that the increased stimulated release of radioactivity was due to [3H]NE. Since the aminopyridines studied also enhanced the release of [3H]NE from atrium treated with cocaine, a blocker of uptake1, it seems likely that the increased release of NE caused by the aminopyridines is due to the enhanced release of NE from sympathetic axon terminals and not to the inhibition of reuptake. It is probable that the sympathomimetic cardiac effects (positive inotropic and chronotropic effect) of aminopyridines observed in animal experiments is due to the increased release of NE, caused by these compounds.     

Prophylactic chemotherapy for hydatidiform mole. Five to 15 years follow-up

The effectiveness of the prophylactic chemotherapy was evaluated in 420 patients with molar pregnancy. All patients were followed for 5 to 15 years after the evacuation. Twenty-two (7.5%) of 293 patients with prophylactic chemotherapy and 23 (18.1%) of 127 patients without prophylactic chemotherapy (control) developed secondary trophoblastic disease. The prophylactic chemotherapy could reduce the occurrence of secondary trophoblastic disease. In these secondary trophoblastic diseases, 5 (22.7%) of 22 patients in the prophylactic chemotherapy group and 5 (21.7%) of 23 in the control had metastatic trophoblastic disease. Choriocarcinoma after the molar pregnancy developed in two patients (0.7%) of the prophylactic chemotherapy group and two (1.6%) of the control. Prophylactic chemotherapy did not eliminate the occurrence of choriocarcinoma. The complication of the prophylactic chemotherapy was seen in 27.3% of the patients. Neither severe complication nor death were related to the toxicity.     

Clinical features of NSAID-induced small intestinal damage

Various factors have been shown to be involved in the pathophysiology of NSAID-induced small intestinal damage. Recent advances in diagnostic methods including video capsule endoscopy and double-balloon endoscopy have enabled us to examine the entire small intestine, and we now recognize that prevalence of small intestinal damage in patients taking NSAIDs is high. NSAIDs cause intestinal damage including redness, erosions, and ulcers in both jejunum and ileum. Most of patients with intestinal pathology are asymptomatic, although a few patients present with iron deficiency anemia and/or hypoalbuminaemia. The risk factors for NSAID-induced enteropathy are unknown. Experimental and clinical studies would unravel the mechanism by which NSAIDs injure intestinal mucosa.