Effect of ACTH,adrenalectomy and the combination treatment on the density of 5-HT2 receptor binding sites in neocortex of rat forebrain and 5-HT2 receptor-mediated wet-dog shake behaviors

The effect of ACTH and/or adrenalectomy on serotonin (5-HT)₂ receptor binding sites was evaluated in the neocortex of rat forebrain. One day after the adrenalectomy or sham operation, ACTH (50 µg/day) was injected subcutaneously into adult male SD rats for 10 consecutive days. Saturation analysis showed that subchronic ACTH treatment significantly increased the B_max values for³H-ketanserin binding without any change in the K_d values. Moreover, this ACTH-induced increase in the B_max values was prevented by adrenalectomy. The concentrations of 5-HT and 5-hydroxyindole acetic acid (5-HIAA) measured by HPLC-ECD were not altered by these manipulations. Ten-day administration of corticosterone (20 and 50 mg/kg) also increased 5-HT₂ receptor density in the neocortex of rat forebrain. 5-HT₂ (and 5-HT_1C) receptor agonist, (±)DOI-induced wet-dog shakes in ACTH and/or adrenalectomy-treated rats were also examined. Ten-day administration of ACTH enhanced (±)DOI-induced wet-dog shakes and this increase was prevented by adrenalectomy. These results indicate that subchronic adrenocorticotropinadrenal axis activation of rats increases both the number of 5-HT₂ receptors in neocortex of forebrain and the wet-dog shake responses induced by (±)DOI.     

Maintenance of Androgen-, Glucocorticoid- or Estrogen-responsive Growth in Shionogi Carcinoma 115 Subline Sustained in Castrated Mice with High Dose of Estrogen for 30 Generations (3 Years)

Shionogi carcinoma 115 (SC115), an androgen-dependent mouse mammary tumor, rapidly loses its androgen responsiveness after androgen withdrawal. The growth of this tumor can also be stimulated by high doses of estrogen or glucocorticoid. In the present study, the maintenance of hormone-responsive growth of SC115 tumors with a high dose of estrogen was examined in castrated male mice using an SCI 15 subline obtained by serial transplantations of SCI 15 tumors in estrogen-treated castrated mice for 3 years (30 generations) (subline E₂). Seed tumors from both SC115 and subline E₂ could rapidly grow in castrated mice given daily injections of testosterone propionate (TP), 17β-estradiol (E₂), or dexamethasone (Dex) (100 μg/mouse/day) but not in those given vehicle alone. Although SCI 15 and subline-E₂ tumors grown with TP or Dex showed temporary regression after steroid withdrawal, the tumors grown with E₂ did not show such temporary regression. The TP-, E₂-, or Dex-induced growth of subline-E₂ tumors was almost the same as that of the original SCI 15 tumors. However, responsiveness to androgen, estrogen or glucocorticoid of both tumors disappeared within one passage in steroid-depleted castrated mice. The present findings demonstrate that the loss of responsiveness to androgen as well as to high doses of estrogen or glucocorticoid of SCI 15 tumors can be prevented in castrated mice not only with androgen but also with high doses of estrogen.     

Histamine N-methyltransferase inhibitor potentiates histamine- and antigen-induced airway microvascular leakage in guinea pigs

Background: Histamine N-methyltransferase (HMT) modulates histamine- and antigen-induced bronchoconstriction. However, it is unclear whether vascular permeability evoked by an allergic reaction can be exaggerated by inhibition of HMT activity. Methods: We studied the effects of intravenously injected SKF 91488, a specific HMT inhibitor, on increases in plasma extravasation induced by intravenously injected histamine in unsensitized guinea pigs and by intravenously injected ovalbumin antigen in guinea pigs sensitized to ovalbumin in vivo with Evans blue dye as a marker. Results: Pretreatment with SKF 91488 shifted, in a dose-dependent fashion, the dose-response curves of the leakage of dye to histamine to lower concentrations in the trachea, main bronchi, and nasal mucosa. Likewise, pretreatment with SKF 91488 (20 mg/kg intravenously) significantly increased the leakage of dye induced by ovalbumin antigen (200 μg/kg intravenously) in three parts of the airway (p < 0.05). In contrast to SKF 91488, intravenously injected aminoguanidine, a specific inhibitor of diamine oxidase (16 mg/kg intravenously), did not alter the leakage of dye induced by histamine (from 0.001 μg/kg to 10 μg/kg intravenously) (p > 0.20). HMT activities were observed in the nasal mucosa, as well as in the trachea and main bronchi, as shown in a previous study. Conclusion: These findings suggest that HMT modulates the effects of exogenous histamine and endogenously released histamine induced by antigen challenge on plasma extravasation in the airway in guinea pigs in vivo. (J ALLERGY CLIN IMMUNOL 1995;96:910-6.)     

Light and electron microscopic studies on rat arterial lesions induced by experimental arterial contraction

Summary Experimental contraction was produced in the rat mesenteric arteries and the arterial segments were studied morphologically. When the rat mesenteric artery was exposed in physiological saline solution at 37° C and 2–3 mg of methoxamine hydrochloride (10 mg/ml) was dripped onto it, intense contraction was observed for about 30 min but elevation in blood pressure was slight. During the contraction, numerous vacuoles were seen in the medial smooth muscle cells of the arterial segments, and these vacuoles were shown electron microscopically to have double unit membranes, indicating that they were formed by herniation of a part of the adjacent smooth muscle cell body. In the arteries 1–6 h after the end of the contraction, cellular, nuclear and vacuolar membranes and myofilaments of the medial muscle cells were partially lost. 12–24 h after the contraction the arteries exhibited necrosis and desquamation of endothelial cells and platelet adhesion. In the media, smooth muscle cells were completely deprived of cell membranes, myofilaments, nuclei, intracytoplasmic organelles other than mitochondria, and vacuolar membranes. The cytoplasm was filled with fine granular and granulo-vesicular material, and fibrin insudation was observed in these severely damaged cells. Arterial contraction may be an important factor in the induction of arterial lesions.     

Suppression of eosinophilic airway inflammation by treatment with alpha-galactosylceramide

To clarify the essential role of NKT cells in allergy, we investigated the contribution of NKT cells to the pathogenesis of eosinophilic airway inflammation using alpha-galactosylceramide (alpha-GalCer), a selective ligand for NKT cells. Although continuous administration of alpha-GalCer during ovalbumin (OVA) sensitization increased OVA-specific IgE levels and worsened eosinophil inflammation, a single administration of alpha-GalCer at the time of OVA challenge completely prevented eosinophilic infiltration in wild-type mice. This inhibitory effect of alpha-GalCer was associated with a decrease in airway hyperresponsiveness, an increase in IFN-gamma, and decreases in IL-4, IL-5 and IL-13 levels in the bronchoalveolar lavage fluids. Analysis of lung lymphocytes revealed that production of IFN-gamma increased in NK cells, but not in T or NKT cells, following alpha-GalCer administration. Induction of vascular cell adhesion molecule-1 in the lungs of wild-type mice was also significantly attenuated by treatment with alpha-GalCer. These effects of alpha-GalCer were abrogated in J alpha281-/- mice, which lack NKT cells, and in wild-type mice treated with anti-IFN-gamma Ab. Hence, our data indicate that alpha-GalCer suppresses allergen-induced eosinophilic airway inflammation, possibly by inducing a Th1 bias that results in inhibition of eosinophil adhesion to the lung vessels.     

Thromboembolism in lung cancer patients]

We reviewed 649 primary lung cancer patients with special reference to the occurrence of thromboembolism. Thirteen episodes of thromboembolism were detected in 12 (1.8%) of the 649. Eight of the 12 were men, and their mean age was 63. Adenocarcinoma was the predominant cell type. Most patients had an advanced stage of the disease, but in some in the cancer was at an early stage. In 5 cases, the finding of thromboembolisms led to diagnosis of the lung cancer (38.5%). Anticoagulant therapy was performed in 9 cases, of which 8 responded without serious complication. We emphasize the importance of anticoagulant therapy as a therapy indicated for thromboembolism in patients with lung cancer.     

Assessment of microvessel perfusion of pituitary adenomas: a feasibility study using turbo spin-echo-based intravoxel incoherent motion imaging

European Radiology - To evaluate the feasibility of assessment of microvessel perfusion of pituitary adenomas with intravoxel incoherent motion (IVIM) imaging using single-shot turbo...     

Difference in the characteristics of subjective and objective sleepiness between narcolepsy and essential hypersomnia

The present study was conducted to investigate the difference in the characteristics of daytime sleepiness between narcolepsy and essential hypersomnia and to identify the relationship between the Epworth Sleepiness Scale (ESS) and the Multiple Sleep Latency Test (MSLT) in patients with these two disorders. Subjects consisted of 34 patients with essential hypersomnia (32.4 +/- 11.0 years old), 52 patients with narcolepsy (29.0 +/- 13.8 years old), and 45 control subjects (33.3 +/- 6.6 years old). The subjects completed the ESS and underwent MSLT following a regular sleep-wake schedule for over 2 weeks. The ESS scores were pathologically high and mean sleep latency on MSLT was short, not only in narcolepsy but also in essential hypersomnia. With respect to sleep latencies on each MSLT session, both essential hypersomnia and control subjects had the smallest value at 14:00, while narcolepsy lacked any statistical change at this time period. The correlation between ESS and mean sleep latency on MSLT was higher in essential hypersomnia than in narcolepsy, and the correlation was strongest for the session performed at 14:00. Based on the ESS and MSLT results, the severity of excessive daytime sleepiness was significantly milder in essential hypersomnia compared with that in narcolepsy. The results also indicate that diurnal variation of sleepiness was maintained, and the correlation between subjective and objective sleepiness was relatively maintained in essential hypersomnia compared to narcolepsy. It is suggested that the mild disease severity of essential hypersomnia contributed to the formation of these characteristics.     

Detection of bone marrow and extramedullary involvement in patients with non-Hodgkin’s lymphoma by whole-body MRI: comparison with bone and <Superscript>67</Superscript>Ga scintigraphies

The aim of this study was to evaluate the diagnostic potential of whole-body MRI (WB-MRI) for the detection of bone marrow and extramedullary involvement in patients with non-Hodgkins lymphoma. WB-MRI, which was performed on 34 patients, consisted of the recording of T1-weighted spin-echo images and a fast STIR sequence covering the entire skeleton. The WB-MRI findings for bone marrow and extramedullary involvement were compared with those from ⁶⁷Ga and bone scintigraphies and bone marrow biopsy results. Two MRI specialists reviewed the WB-MRI results and two expert radiologists in the field of nuclear medicine reviewed the bone and ⁶⁷Ga scintigraphy findings. Bone marrow and extramedullary involvement of non-Hodgkins lymphoma were confirmed by follow-up radiographs and CT and/or a histological biopsy. The detection rate of WB-MRI was high. More bone marrow involvement was detected by biopsy, and more lesions were detected by scintigraphies. In total, 89 lesions were detected by WB-MRI, whereas 15 were found by biopsy, 5 by ⁶⁷Ga scintigraphy, and 14 by bone scintigraphy. WB-MRI could also detect more extramedullary lesions than ⁶⁷Ga scintigraphy; i.e., 72 lesions were detected by WB-MRI, whereas 54 were discovered by ⁶⁷Ga scintigraphy. WB-MRI is useful for evaluating the involvement of bone marrow and extramedullary lesions throughout the skeleton in patients with non-Hodgkins lymphoma.