Regulation of cerebral blood flow in the hippocampus by neuronal activation through the perforant path: relationship between hippocampal blood flow and neuronal plasticity.

Although changes in regional cerebral blood flow (rCBF) have been used as an index of neuronal activity, the effects of long-term potentiation (LTP) in the hippocampus, widely assumed to be an electrophysiological basis of learning and memory, on the changes in rCBF by neuronal activity remain unclear. Hence, to elucidate whether the effects of LTP in the hippocampus reflect in the correlation between neuronal activity and co-occurring changes in rCBF, we investigated the effects of LTP on the responses of hippocampal blood flow (HBF) to the electrical stimulation of the perforant path in vivo. We continuously measured HBF using Laser-Doppler flowmetry, and systemic blood pressure and heart rate were measured from the femoral artery during electrical stimulations in halothane-anesthetized rats. The results showed that the reactivity of HBF to neuronal activation was potentiated by a tetanic stimulation that induces LTP, although the tetanic stimulation did not affect baseline of HBF values. These results suggest that the presence of the plasticity between neuronal activity and the rCBF in the perforant path-dentate pathway, and the neuronal plasticity can be reflected in the transient changes in rCBF when the brain region is activated but not in the steady state.

Liposome-encapsulated hemoglobin ameliorates impairment of fear memory and hippocampal dysfunction after cerebral ischemia in rats.

Liposome-encapsulated hemoglobin (LEH) has been developed as a blood substitute. In spite of its size (1/30 - 1/40 of erythrocytes), LEH has an oxygen-carrying capacity comparable to erythrocytes. Thus, LEH is expected to carry oxygen into vital organs via collateral routes during ischemia induced by vascular embolism. In the present study, we examined the therapeutic effects of LEH on behavioral impairments in rats after four-vessel occlusion (4VO) for 30 min. In the open-field test, locomotor activity in 4VO rats did not alter 7 days after ischemia. However, in the contextual fear conditioning (CFC) test, the freezing rate was significantly decreased in 4VO rats, although no behavioral changes in the Y-maze test and elevated plus-maze test were observed. Phosphorylation of the cyclic AMP response element-binding protein (CREB) in the hippocampal CA1 region after the CFC test was attenuated. These 4VO-induced impairments were significantly alleviated by the administration of LEH (5 ml/kg, i.v.) during occlusion. Moreover, LEH did not alter hippocampal blood flow and tissue oxygen pressure during 4VO, but it did suppress hyperoxia after ischemia-reperfusion. These findings suggest that LEH, an artificial oxygen carrier, could be a novel therapeutic agent for brain dysfunction after acute cerebral ischemia.

[Three cases of second primary lung cancer after radiotherapy for breast cancer].

We report three cases of primary lung cancer after radiotherapy for breast cancer. Case 1 was a 73-year-old woman, who had bilateral breast cancer 27 years previously. Case 2 was a 70-year-old woman, who had left breast cancer 31 years previously. Case 3 was a 56-year-old woman, who had left breast cancer 14 years previously. Since all three lung cancers developed within the irradiated field, breast cancer radiotherapy was speculated to be one of the contributing factors for their lung cancers. Clinicians treating breast cancer survivors who have received Cobalt-60 radiation therapy and are or have been smokers should be aware of the risk of lung cancer over 10 years or more after radiotherapy.

[A case of Lambert-Eaton myasthenic syndrome with small cell lung cancer, treated with 3,4-diaminopyridine].

A 77-year-old man was admitted to our hospital with muscle weakness and shortness of breath. Chest CT showed a mass in the left upper lobe, and electromyography showed waxing phenomenon with high-frequency repetitive stimulation. We diagnosed Lambert-Eaton myasthenic syndrome accompanying small cell lung cancer. He was treated with carboplatin and etoposide, and concurrent thoracic irradiation. Although, the tumor size decreased, his myasthenic symptoms remained. He started taking 3,4-diaminopyridine and his muscle weakness improved dramatically, and he was eventually able to walk finally. In some cases, anti-tumor therapies cannot improve the myasthenic symptoms. In such cases, 3,4-diaminopyridine could improve the quality of life, and should be approved in Japan.

[A case of pulmonary pleomorphic carcinoma with epidermal growth factor receptor (EGFR) mutation].

A 70-year-old woman with cough was diagnosed with pulmonary adenocarcinoma by bronchoscopic transbronchial biopsy. She was diagnosed cT2N0M0, stage IB clinically, and the tumor was surgically resected. Postoperative pathology was confirmed to be pleomorphic carcinoma of pT2N2M0, stage III A. She received 6 courses of adjuvant chemotherapy consisting of cisplatin and docetaxel. Five months later, new pulmonary and bone metastases were detected. Gefitinib was started, and she has shown stable disease for 7 months. Epidermal growth factor receptor (EGFR) mutation was observed in her tumor specimens.

Expression of secretoglobin3A2 (SCGB3A2) in primary pulmonary carcinomas.

Secretoglobin (SCGB) 3A2 is a downstream target gene for the thyroid transcription factor-1 (TITF1). SCGB3A2 plays a role as an anti-inflammatory agent, however, its role in primary pulmonary carcinomas has not been examined. We assessed immunohistochemical expression of SCGB3A2 in primary pulmonary carcinomas and evaluated the correlation between the expression and histopathological phenotypes and prognosis. One hundred and fifty-six primary lung cancers undergone for surgical resection were examined. The percentages of SCGB3A2 positive cells were scored and tumors had immunoreactivity in more than 10% of tumor cells were considered positive for SCGB3A2. Overall reactivity for SCGB3A2 was observed in 116 (74.4%) of 156 primary lung cancers. SCGB3A2 was predominantly expressed in adenocarcinomas (86.5%), compared with squamous cell carcinomas (50.0%) and small cell carcinomas (42.9%). The expression in papillary adenocarcinomas was seen at higher frequency than that in tubular adenocarcinomas. There was no significant relationship between SCGB3A2 expression and tumor differentiation, and pathological stage. Positive expression of SCGB3A2 was not associated with better survival rate. SCGB3A2 expression in primary pulmonary carcinomas is high, especially in adenocarcinomas. Our results indicate that SCGB3A2 has a potential to be a specific and useful marker for primary pulmonary adenocarcinomas.

A virtual bronchoscopic navigation system under X-ray fluoroscopy for transbronchial diagnosis of small peripheral pulmonary lesions.

We had reported the utility of virtual bronchoscopic navigation system under CT-guidance for the diagnosis of small peripheral pulmonary lesions (PPLs). This study investigated the efficacy of virtual bronchoscopic navigation system for the diagnosis of small PPLs under X-ray fluoroscopy. We performed bronchoscopy with this system for 94 consecutive patients with 96 PPLs (< or =30mm in longest diameter; mean longest diameter, 16.2mm). A standard bronchoscope was used in 38 cases, and an ultrathin bronchoscope in 58 cases. Virtual bronchoscopic images were reconstructed from helical CT data. All the examinations were performed under X-ray fluoroscopy with virtual bronchoscopic navigation system, we referred both virtual bronchoscopic images and actual bronchoscopic images simultaneously to navigate the bronchoscopic pathway to the PPLs. Specimens for pathological examination were collected by transbronchial biopsy (TBB) and/or brushing. Virtual images accorded well with actual bronchoscopic images. The average total examination time was 24.1+/-7.4min (mean+/-S.D.). The overall diagnostic yields were 62.5% (60 of 96 PPLs), 71.1% (27 of 38 PPLs) with the standard bronchoscope, and 56.9% (33 of 58 PPLs) with the ultrathin bronchoscope. Diagnostic rates were 35%, 61.4% and 94.7% for lesions < or =10, 10-20, and >20mm, respectively. There were eight ground glass opacity (GGO) lesions confirmed only on CT scans; seven cases were pathologically diagnosed. All the examinations were performed safely with no complications. Bronchoscopy with virtual bronchoscopic navigation under X-ray fluoroscopy is useful for the diagnosis of small PPLs.

[A case of advanced double cancer of the lung and stomach responding to combination chemotherapy of cisplatin and TS-1].

A 76-year-old male patient was diagnosed with advanced double cancer of the lung and stomach. He had also been suffering from interstitial pneumonitis for several years. He was treated with combination of cisplatin and TS-1. TS-1 (120 mg/body/day) was administered for 21 days from day 1, and cisplatin (60 mg/m(2)) was given on day 8 followed by a 14-days interval. After two courses of chemotherapy,the dose of cisplatin was reduced to 48 mg/m(2) because of grade 1 serum creatinine elevation. The lesions of the lung and stomach were improved significantly without exacerbation of the interstitial pneumonitis.

Exhaled nitric oxide as a marker of airway inflammation for an epidemiologic study in schoolchildren.

BACKGROUND: Exhaled nitric oxide (eNO) levels are increased in airway inflammatory disorders, such as asthma. OBJECTIVE: We sought to determine whether eNO could serve as a noninvasive marker of allergic airway inflammation for an epidemiologic study in schoolchildren. METHODS: Two hundred seventy-eight schoolchildren aged 10 to 12 years answered a modified American Thoracic Society questionnaire, and eNO levels and pulmonary function were measured. In 246 subjects serum nonspecific IgE levels and levels of IgE specific to house dust mite, cat, cedar, and mold were also measured. Correlation analysis was used to examine eNO levels, nonspecific IgE levels, antigen-specific IgE levels, and pulmonary function. In addition, we compared these variables between subjects with (recurrent wheezers) and without (nonwheezers) recurrent wheeze. Finally, multiple logistic regression analysis was used to find possible predictors for recurrent wheezers. RESULTS: eNO showed significant positive correlations with nonspecific IgE (r=0.62, P <.001) and mite-specific IgE (r=0.74, P <.001) and weak positive correlations with specific IgE to cat and cedar. Only eNO showed a weak but significant inverse correlation with pulmonary function (%FEV(1), P=.035; FEV(1)/forced vital capacity, P=.018). eNO, nonspecific IgE, and mite-specific IgE levels in recurrent wheezers were greater (P <.001), and %FEV(1) was less (P=.06) when compared with values seen in nonwheezers. Finally, eNO was determined by means of multiple logistic regression analysis to be the best predictor for recurrent wheezers compared with other variables (odds ratio, 11.2; 95% CI, 1.33-94.0). CONCLUSION: eNO can be used in epidemiologic studies as a noninvasive marker of allergic airway inflammation in schoolchildren.