Participation of Ia reciprocal inhibitory neurons in the spinal circuitry of the tonic neck reflex

Summary As part of our studies of the spinal circuitry of the tonic neck reflex, we have recorded extracellularly from Ia reciprocal inhibitory neurons of the decerebrate, labyrinthectomized cat. The activity of a majority of neurons driven by stimulation of the quadriceps nerve was modulated by sinusoidal rotation of the neck; such modulation was much less frequent in the case of neurons driven by stimulation of nerves to more distal muscles. The results suggest that some of the inhibition which is part of the tonic neck reflex is mediated by Ia reciprocal inhibitory neurons, but that other pathways must also play an important role.     

Negative chronotropic actions of endothelin-1 on rabbit sinoatrial node pacemaker cells

1. The effects of endothelin-1 (ET-1) on sinoatrial (SA) node preparations of the rabbit heart were studied by means of whole-cell clamp techniques.
2. ET-1 at 1 nM slowed the spontaneous beating activity and rendered half of the cells quiescent. At a higher concentration of 10 nM, the slowing and cessation of spontaneous activity were accompanied by hyperpolarization.
3. In voltage-clamp experiments, ET-1 decreased the basal L-type Ca²⁺ current (I_Ca(L)) dose-dependently with a half-maximal inhibitory concentration (EC₅₀) of 0.42 nM and maximal inhibitory response (E_max) of 49.5%. The delayed rectifying K⁺ current (I_K) was also reduced by 33.2±11.1% at 1 nM. In addition, an inwardly rectifying K⁺ current was activated by ET-1 at higher concentrations (EC₅₀=4.8 nM). These ET-1-induced changes in membrane currents were abolished by BQ485 (0.3 μM), a highly selective ET_A receptor antagonist.
4. When I_Ca(L) was inhibited by ET-1 (1 nM), subsequent application of 10 μM ACh showed no additional decrease in I_Ca(L), suggesting the involvement of cyclic AMP in the effects of ET-1 on I_Ca(L). In contrast, 1 nM ET-1 further decreased I_Ca(L) in the presence of 10 μM ACh, suggesting that ET-1 activates some additional mechanism(s) which inhibit I_Ca(L). The ET-1-induced I_Ca(L) inhibition was abolished by protein kinase A inhibitory peptide (PKI, 20 μM) or H-89 (5 μM). However, the I_Ca(L) inhibition was not affected by methylene blue (10 μM), suggesting a minor role for cyclic GMP in the effect of ET-1 under basal conditions.
5. ET-1 failed to inhibit I_Ca(L) when the pipette contained GDPβS (200 μM). However, incubation of the cells with pertussis toxin (PTX, 5 μg ml⁻¹, >6 h) only reduced the ET-1-induced inhibition to 21.5±9.5%, whereas it abolished the inhibitory effect of ACh on I_Ca(L).
6. Intracellular perfusion of 8-bromo cyclicAMP (8-Br cyclicAMP, 500 μM) attenuated, but did not abolish the inhibitory effect of ET-1 on I_Ca(L). This 8-Br cyclicAMP-resistant component (17.5±14.4%, n=20) was not affected by combined application of 8-Br cyclicAMP with 8-bromo cyclicGMP (500 μM), ryanodine (1 μM) or phorbol-12-myristate-13-acetate (TPA; 50 nM).
7. In summary, ET-1 exerts negative chronotropic effects on the SA node via ET_A-receptors. ET-1 inhibits both I_Ca(L) and I_K, and increases background K⁺ current. The inhibition of I_Ca(L) by ET-1 is mainly due to reduction of the cyclicAMP levels via PTX-sensitive G protein, but some other mechanism(s) also seems to be operative.

     

Precancerous lesions of the stomach

The etiology of stomach cancer in relation to preexisting mucosal alterations is described and discussed from a review of the literature and our own previously reported experience. The incidence of cancerization or malignant change of gastric polyp, chronic gastric ulcer, and chronic gastritis varies considerably from researcher to researcher. Clinical follow-up studies in many cases of gastric polyp and chronic ulcer discovered in the mass survey examination of the stomach revealed incidences of malignant degeneration of 2.3% of the gastric polyp cases and 2.06% of the gastric ulcer cases.

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Résumé Les relations entre altérations préexistantes de la muqueuse et étiologie du cancer gastrique sont décrites et discutées, avec revue de la littérature et de notre expérience personnelle. La fréquence des cancérisations ou des dégénérescences malignes des polypes gastriques, de l'ulcère gastrique chronique et de la gastrite chronique est éminemment variable d'une étude à l'autre. Les follow-up de populations soumises à des examens systématiques de dépistage indiquent que la fréquence des dégénérescences malignes est de 2.3% pour les polypes gastriques et de 2.06% pour l'ulcère gastrique.

     

Radiation tolerance of the cochlear nerve at the γ-knife in rabbits

Since the first treatment of acoustic neurinoma using the γ-knife by Leksell, a series of cases have been reported with good control rates. However, the most frequent complication is delayed hearing loss which occurs in more than 50% of patients. The purpose of this study was to define a safe dose by analyzing the radiosurgical dose-response relationship and histological effects on the normal cochlear nerve in rabbit. The rabbits had computed tomography (CT)-guided stereotactic radiosurgery on their cochlear nerves in the internal auditory canal with a 4 mm collimator focusing of a γ-unit. Maximum doses of 10, 20, 30, 40, 60, 80, 100, 200 and 500 Gy were administered. After the radiosurgery, auditory brain stem responses (ABR) and the behavior of the rabbits were evaluated periodically. At the conclusion, histological investigations were performed. No physiological or histological findings were observed from doses of 30 Gy or below during the 12 month period after the radiosurgery. A dose of 100 Gy caused a severe ABR threshold elevation, vestibular dysfunction and facial palsy. Necrosis and demyelination of nerves were observed pathologically. In this study, we determined that the safe dose to the normal cochlear nerve during radiosurgery was under 40 Gy in rabbits, and complications seemed to vary due to individual differences in radiation tolerance.     

Statistical Analysis of Factors Affecting the Outcome of Patients with Ruptured Distal Anterior Cerebral Artery Aneurysms

Summary  The clinical factors affecting the outcome of patients with ruptured distal anterior cerebral artery (ACA) aneurysms were analyzed using multiple logistic regression analysis.  The medical records were reviewed of 52 patients (57 aneurysms) with ruptured distal ACA aneurysms operated on by the same neurosurgeon over 25 years. The standard policy was early surgery for patients in Hunt and Kosnik grades I to IV. Age, sex, Hunt and Kosnik grade, timing of operation, size of aneurysms, number of aneurysms, association of intracerebral haemorrhage (ICH), intraventricular haemorrhage, and azygos ACA, use of temporary clipping , occurrence of premature rupture, and presence of psychiatric change were investigated. Univariant analysis disclosed that clinical grade (P=0.0006), size of aneurysm (P=0.005), and size of ICH (P=0.012) affected the outcome of patients. Multiple logistic regression analysis found that Hunt and Kosnik grade (P=0.010) and timing of operation (P=0.033) affected the outcome. There was no significant relationship between long-term outcome and clinical factors, although a close relationship was found with Hunt and Kosnik grade (P=0.071).  Clinical grade and timing of the operation affected the outcome of patients with ruptured distal ACA aneurysms. Patients harboring ICH of over 3 cm diameter in poor grades should also be carefully treated.     

Recombinant human betacellulin promotes the neogenesis of beta-cells and ameliorates glucose intolerance in mice with diabetes induced by selective alloxan perfusion

Betacellulin (BTC), a member of the epidermal growth factor family, is expressed predominantly in the human pancreas and induces the differentiation of a pancreatic acinar cell line (AR42J) into insulin-secreting cells, suggesting that BTC has a physiologically important role in the endocrine pancreas. In this study, we examined the in vivo effect of recombinant human BTC (rhBTC) on glucose intolerance and pancreatic morphology using a new mouse model with glucose intolerance induced by selective alloxan perfusion. RhBTC (1 microg/g body wt) or saline was injected subcutaneously every day from the day after alloxan treatment. The intraperitoneal glucose tolerance test revealed no difference between rhBTC-treated and rhBTC-untreated glucose-intolerant mice at 2-4 weeks. However, glucose tolerance was significantly improved and body weight was significantly increased in rhBTC-treated mice compared with untreated mice at 8 weeks. Islet-like cell clusters, consisting mainly of beta-cells, were increased in the pancreas and were localized in contact with the ductal lining cells and sometimes with acinar cells. In conclusion, administration of rhBTC improved glucose tolerance in this mouse model by increasing beta-cell volume, primarily through accelerated neogenesis from ductal lining cells.     

A case of pulmonary cavernous hemangioma: immunohistological examination revealed its endothelial cell origin

A 29-year-old woman was referred to our hospital for an abnormal shadow on chest roentgenogram. She had no symptom but its shadow was pointed out about 20 years ago. Chest CT scan showed a sharply demarcated homogenous mass measured 10 x 10 mm in the S4 segment. The tumor was resected with video-assisted thoracoscopic surgery under CT-guided marking wire inserted. Microscopic examination suspected cavernous hemangioma. Immunohistological staining demonstrated most lining cells of the cavernous structure stained positively for von Willebrand factor antibody, which suggests that this tumor was associated with endothelium. Then we decided that this tumor was pulmonary cavernous hemangioma.