Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats.

We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells.     

Pulmonary surfactant proteins and lipids as modulators of inflammation and innate immunity

Objectives: The pulmonary surfactant system of the human lung consists of unique lipids and proteins that contribute to the biophysical and innate immune properties of the organ. Surfactant protein A (SP‐A) is an oligomeric protein consisting of 18 protomers with collagen and lectin–like domains that recognizes glycoconjugates, lipids and protein determinants on both host cells and invading microorganisms. The authors examined the interaction of SP‐A with Mycoplasma pneumoniae and the influence of the protein upon the innate immune response to the bacteria. Methodology: The authors quantified SP‐A interaction with bacteria using ELISA, and identified the major surface ligand by thin layer chromatography, HPLC and mass spectrometry. The inflammatory response of human and rat macrophages was measured by quantifying tumour necrosis factor‐α secretion using ELISA, and nitric oxide production. Results: SP‐A bound the bacteria with high affinity and enhanced the inflammatory response of human and rat macrophages to the organism and its membranes. Analysis of the interaction of SP‐A with the bacteria revealed that the major ligand was a phospholipid. The lipid ligand was purified by a combination of thin layer and HPLC, and identified by mass spectrometry. The mass spectrometry demonstrated that the SP‐A reactive lipid consisted of several disaturated molecular species of phosphatidylglycerol (PtdGro). Additional experiments were performed to determine if disaturated PtdGro was capable of interfering with the action of SP‐A as an inhibitor of bacterial lipopolysaccharide‐induced inflammatory mediator production by macrophages. The disaturated PtdGro failed to alter the anti‐inflammatory action of SP‐A but unexpectedly these same studies revealed that unsaturated PtdGro can modify the host response to lipopolysaccharide. Conclusions: These findings reveal that both the lipids and proteins of pulmonary surfactant play a role in regulating the host response to invading microorganisms.     

Treatment of tardive dyskinesia with ceruletide

1. Seven patients with TD were treated with a single dose of ceruletide 0.8 microgram/kg i.m. 2. EMG and MV were recorded, and the average power spectrum was computed. 3. Effect of ceruletide on TD within 2 hr after injection was varied (3 cases: inhibitory, 2 cases: facilitatory, 2 cases: no effect). 4. Two patients with severe TD, who showed improvement after a single administration, received repeated administration of ceruletide (0.6 microgram/kg i.m.) and their TD symptoms were recorded on videotape for blind consensus ratings. In both patients ceruletide caused a marked decrease in severity of TD, and the effects lasted for several weeks. 5. The present findings might contribute to further understanding of the role of CCK in the brain and to the treatment of TD.     

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.     

Intrapulmonary Schwannoma

A 58-year-old woman was admitted due to an abnormal shadow on chest X-ray, without any symptoms. Chest computed tomography showed a round mass in the anterior segment of the right upper lobe. Segmentectomy was performed and histopathological examination revealed a primary neurogenic tumor of Schwann cell origin. Immunohistochemical staining demonstrated the presence of S-100 protein in the tumor cells. We present a case of intrapulmonary schwannoma and review 62 cases of primary schwannoma of the lung.     

Comparison of transfer and distribution of technetium and rhenium in radish plants from nutrient solution

Tracer experiments were carried out to compare the plant uptake behavior of Tc and Re from nutrient solutions. Radish plants, transplanted to nutrient solution including various tracers, showed the same uptake and distribution of ^95mTc and ¹⁸³Re. The trend was the same when the ⁹⁹Tc and stable-Re concentrations were increased in nutrient solution. The behavior of other elements was different from that of Tc and Re. These findings suggest the possible use of Re as the chemical analogue of Tc in soil solution to plant uptake experiments.     

ENDOSCOPIC MUCOSAL RESECTION AND SUBMUCOSAL DISSECTION METHOD FOR LARGE COLORECTAL TUMORS

The goal of endoscopic mucosal resection (EMR) is to allow the endoscopist to obtain tissue or resect lesions not previously amenable to standard biopsy or excisional techniques and to remove malignant lesions without open surgery. In this article, we describe the results of conventional EMR and EMR using an insulation‐tipped (IT) electrosurgical knife (submucosal dissection method) for large colorectal mucosal neoplasms and discuss the problems and future prospects of these procedures. At present, conventional EMR is much more feasible than EMR using IT‐knife from the perspectives of time, money, complication, and organ preservation. However, larger lesions tend to be resected in a piecemeal fashion; and it is difficult to confirm whether EMR has been complete. For accurate histopathological assessment of the resected specimen en bloc EMR is desirable although further experience is needed to establish its safety and efficacy. Further improvements of in EMR with special knife techniques are required to simply and safely remove large colorectal neoplasms.     

Long-term survival of a pulmonary artery sarcoma produced by aggressive surgical resection and adjuvant chemoradiotherapy.

Malignant pulmonary artery tumors represented by sarcomas are rare, but fatal. Early diagnosis and radical surgical resection offer the only chance for survival. However, surgical intervention has some challenging aspects, and prognosis is poor even after tumor resection. We report a case of a pulmonary artery sarcoma between the right ventricular outflow tract and the pulmonary artery branches. The tumor was aggressively extracted with reconstruction using a cryopreserved pulmonary valved allograft, followed by adjuvant chemoradiotherapy. At 56 months after surgery, the patient is well without any evidence of recurrence, demonstrating that aggressive surgical resection with adjuvant chemoradiotherapy can prolong survival.     

International project--MGTX study]

MGTX Study is a multi-center, international, single-blinded, randomized trial to determine whether extended transsternal thymectomy (ETTX) for patients with myasthenia gravis receiving the prednisone protocol confers added benefits to the prednisone protocol alone. The aims of the study are answering following three questions. 1) Does ETTX combined with prednisone result in a greater improvement in myasthenic weakness, compared to prednisone alone? 2) Does ETTX combined with prednisone result in a lower total dose of prednisone, thus decreasing the likelihood of concurrent and long-term toxic effects, compared to prednisone alone? 3) Does ETTX combined with prednisone enhance quality of life by reducing adverse events and symptoms associated with the therapies, compared to prednisone alone? Primary outcome measure is consists with 1) Comparison of the prednisone protocol alone to prednisone protocol plus ETTX, based on the clinical response to therapy measured over the 3 year trial period by the Area Under the Quantitative Myasthenia Gravis (QMG) Weakness Score (AUQMG), and 2) Testing the difference in the total prednisone used over the 3 year trial period measured by pill count from blister packs (Area Under the Prednisone Dose Time Curve, AUDTC), conditional on the results of comparing AUQMG.     

Pulmonary injury by an over-the-counter drug, Nospole G]

A 78-year-old woman was admitted with dyspnea. She had caught a cold and took an over-the-counter drug (Nospole G) for 2 weeks before admission. Chest radiography and CT scanning showed bilateral diffuse and interstitial shadows, and arterial blood gas analysis demonstrated severe hypoxemia. Withdrawal of Nospole and treatment with both corticosteroid and sivelestat sodium resulted in improvement of clinical findings and successful recovery from mechanical ventilation. A drug lymphocyte stimulation test for Nospole G was positive. Based on these findings, we determined that this patient had drug-induced pneumonitis caused by Nospole G. Finally, she died of sepsis caused by multidrug-resistant Staphylococcus aureus (MRSA) infection. In summary, we report here an elderly case of drug-induced pneumonitis successfully weaned from mechanical ventilation by early treatment with corticosteroid and sivelestat sodium, monitored by changes of markers for interstitial pneumonitis (KL-6, SP-A, SP-D).