Impact of five SNPs in dopamine-related genes on executive function.

OBJECTIVES: Dopamine neurotransmission is a critical factor for executive function, which is controlled by the prefrontal cortex in humans. Although the contribution of genetic factors to the regulation of brain dopaminergic activity is widely acknowledged, identification of a genotype-phenotype association has not yet been clearly established. In this study, we therefore evaluated the effects of five functional single-nucleotide polymorphisms (SNPs) in specific genes related to dopamine neurotransmission on executive function in a general population. MATERIALS AND METHODS: Participants of the health examination at the Shimane Institute of Health Science were recruited for this study (n = 964). To evaluate executive function, the Frontal Assessment Battery (FAB) was administered. SNPs were genotyped using the TaqMan method. RESULTS: A significant association was found between an SNP in the catechol-O-methyltransferase (COMT) gene (rs4680) encoding the low-activity Met allele and FAB score (P = 0.003). Of note, the flexibility subset of the FAB was associated with the SNP in COMT (P = 0.003) after adjustment for confounding factors. The generalized multifactor dimensionality reduction method identified that the combination of two SNPs in the COMT gene (rs4680) and the dopamine D4 receptor gene (rs1800955) had a significant effect on FAB score. CONCLUSIONS: Our study indicates a contribution of rs4680 in the COMT gene to the variability in executive function, as assessed by the FAB. In addition, we have indicated that a complex gene-gene interaction between SNPs in the genes related to dopamine neurotransmission may influence executive function in a general population.

[Occurrence of BOOP outside radiation field after radiation therapy for small cell lung cancer].

We report a case of bronchiolitis obliterans organizing pneumonia (BOOP) that occurred outside the radiation field after radiation therapy for small cell lung cancer. A 74-year-old woman received chemotherapy and a total of 60 Gy of radiation therapy to the right hilum and mediastinum for small cell carcinoma of the suprahilar area of the right lung. Radiation pneumonitis developed within the radiation port 3 months after the completion of radiation therapy. She complained of cough and was admitted 7 months after completion of the radiation therapy. Chest radiography and computed tomography demonstrated peripheral alveolar opacities outside the radiation field on the side contralateral to that receiving the radiation therapy. Bronchoalveolar lavage showed that the total cell count was increased, with a markedly increased percentage of lymphocytes. Transbronchial lung biopsy revealed a histologic pattern consistent with BOOP. Treatment with corticosteroids resulted in rapid improvement of the symptoms and complete resolution of the radiographic abnormalities of the left lung. Although some cases of BOOP following radiation therapy for breast cancer have been reported, none of BOOP after radiation therapy for lung cancer have appeared in the literature.

Fatal pulmonary arterial thrombosis associated with chlorine gas poisoning.

We present a patient with accidental chlorine gas poisoning who died from pulmonary thrombosis due to a marked increase in hemostatic factors such as von Willebrand factor after recovering from the acute poisoning.

[Occurrence of BOOP outside radiation field after tangential radiation therapy for breast carcinoma].

We report three cases of bronchiolitis obliterans organizing pneumonia (BOOP) that occurred outside the radiation field after radiation therapy using tangential fields for breast carcinoma. All patients complained of a cough between 14 and 20 weeks after completion of radiation therapy. Fever also developed in two of the three. Chest radiography and computed tomography demonstrated peripheral alveolar opacities outside the radiation field on the same side as the radiation therapy. Laboratory data showed an increased level of C-reactive protein and an increased erythrocyte sedimentation rate. Bronchoalveolar lavage showed an elevated total cell count with a very high percentage of lymphocytes. Transbronchial lung biopsy revealed a histologic pattern consistent with BOOP. Treatment with corticosteroids resulted in rapid clinical improvement and complete resolution of the radiographic abnormalities. This pulmonary disorder appears to be induced by radiation, especially when a tangential field is employed for breast carcinoma, though the etiology has not been fully investigated. It is important to be aware of this type of pulmonary complication in patients given radiotherapy for breast carcinoma.

Increased incidence of autoantibodies to interleukin-1a in rheumatoid arthritis with interstitial lung disease.

OBJECTIVE: To clarify the clinical significance of autoantibodies (auto-Ab) to interleukin-1alpha (IL-1alpha) in rheumatoid arthritis (RA) with interstitial lung disease (ILD), we examined the IL-1alpha auto-Ab level in serum of patients with RA with/without ILD. METHODOLOGY: We investigated the level of IL-1alpha auto-Ab in serum of 70 patients with RA with/without ILD and 40 control patients (CP). Levels of IL-1alpha auto-Ab were measured by radioimmunoassay, and serum was regarded as IL-1alpha auto-Ab positive at an auto-Ab level of more than 5 ng/mL. RESULTS: Interleukin-1alpha auto-Ab was detected in the serum of 30 out of 70 RA patients (42.9%), and six out of 40 CP (15%) (P < 0.05). Interleukin-1alpha auto-Ab were detected in the serum of 18 out of 32 patients with RA with ILD (56.2%) and 12 out of 38 patients with RA without ILD (31.5%). The positive rate of these autoantibodies in RA with ILD was significantly higher than that in RA without ILD (P < 0.05). Although C-reactive protein, immunoglobulin G, rheumatoid factor and rheumatoid arthritis particle agglutination levels in serum from patients with RA with ILD were not significantly different between the IL-1alpha auto-Ab-positive and -negative groups, the lactate dehydrogenase level (LDH) and AaDO, in the IL-1alpha auto-Ab-positive group were significantly higher than those in the negative group (LDH: P < 0.001, AaDO2: P < 0.05). CONCLUSION: These results suggest that IL-1alpha auto-Ab are generated in response to the immunoinflammatory process of ILD in RA, and these autoantibodies may neutralize and regulate the IL-1alpha activity.

Characterization of immunoglobulin binding factor in sputum from patients with chronic airway diseases.

OBJECTIVE: Immunoglobulin binding factor (IgBF) is known to bind immunoglobulin, to interact with anti-Fc gamma-III antibodies and to be present in the lower respiratory tract of normal healthy subjects. In this study, in order to clarify the role of IgBF in respiratory diseases, we investigated whether IgBF exists in the airway of patients with chronic airway diseases. METHODOLOGY: IgBF was measured in the sputum of 28 normal subjects and 59 patients with chronic airway diseases including 37 cases of chronic bronchitis, 18 bronchiectasis, and four diffuse panbronchiolitis by enzyme-linked immunosorbent assay. RESULTS: Immunoglobulin binding factor concentration in the sputum of patients with chronic airway diseases (purulent sputum, 50.2 +/- 8.2 microg/mL; mucoid sputum, 88.6 +/- 12.8 microg/mL) was higher than that in induced sputum of normal subjects (6.3 +/- 5.5 microg/mL; P < 0.001). Immunoglobulin binding factor level in mucoid sputum was significantly higher than that in purulent sputum (P < 0.05). A significant inverse correlation was shown between the IgBF level and the elastase activity in sputum, and the concentration of IgBF purified from seminal plasma was decreased by treatment with neutrophil elastase, indicating that IgBF might be degraded by elastase. In the gel filtration chromatography of both types of sputum, IgBF was eluted in a region corresponding to a molecular weight of 27 kDa as a single peak. Western blot analysis with a monoclonal antibody to IgBF indicated that IgBF in both types of sputum had a molecular weight of 27 kDa under non-reducing conditions and of 16 kDa under reducing conditions. CONCLUSION: These results demonstrate that a high level of IgBF is present in the respiratory tract of patients with chronic airway diseases and may be related to the pathogenesis of these diseases.

A case of resectable lung adenocarcinoma associated with sarcoidosis.

A 71-year-old woman with uveitis was referred to our hospital for further examination of the possible underlying diseases. In roentgenological examination with plain X-ray and CT scan, hilar and mediastinal lymphadenopathy and a mass shadow in the right upper lung field was observed, whereas fibrotic changes were not obvious in both lung fields. Transbronchial lung biopsy with fiberoptic bronchoscope revealed granulomatous interstitial pneumonia. CD4-positive lymphocytes were increased in bronchoalveolar lavage. The patient was diagnosed as having sarcoidosis. Subsequently, right upper lobectomy was performed, and Stage I lung adenocarcinoma was diagnosed. The patient is under follow up without medication and the disease has been stable for two years. A relationship between epithelioid granulomatosis and malignant diseases is discussed and a review of the literature is given. Since it is still controversial as to the incidence of malignant diseases in sarcoidosis patients, it is important to accumulate data on these associations.

Decreased prostaglandin E2 synthesis by lung fibroblasts isolated from rats with bleomycin-induced lung fibrosis.

In order to clarify the mechanism of pulmonary fibrosis, we examined the functional changes of lung fibroblasts in bleomycin (BLM)-induced pulmonary fibrosis. Lung fibroblastic cells were obtained from rat lungs after an intratracheal treatment of BLM or saline. The spontaneous proliferation of BLM-treated rat fibroblasts (BRF), which was estimated by 3H-TdR incorporation and direct cell counting, was significantly more rapid than that of normal saline-treated rat fibroblasts (NRF). Next, we investigated prostaglandin (PG) E2 synthesis by BRF and NRF, with or without stimulation by interleukin (IL)-1 alpha, and found that PGE2 production by BRF was significantly less than that by NRF. There was no significant difference in cyclooxygenase (COX) activity and COX-2 mRNA level between BRF and NRF, indicating that the change in PGE2 production was independent of COX, a rate-limiting enzyme for the production of PGE2. These results suggest that the proliferation of fibroblasts is down-regulated by PGE2 released from themselves in normal lungs in an autocrine fashion, thus the decreased PGE2 production observed in lung fibroblasts from rats with BLM-induced pulmonary fibrosis may result in the excessive fibroblast proliferation in this disorder. Overall, these findings throw some light on the mechanism of development of BLM-induced pulmonary fibrosis.

Sarcoidosis associated with acute renal failure and increased levels of interleukin-6 in urine.

A 24-year-old man who had uveitis and showed intrathoracic lymph node swelling on a chest X-ray, was admitted to our hospital for further examination. Transbronchial lung biopsy specimens revealed non-caseating granulomas compatible to sarcoidosis. As the renal function became progressively worse, a specimen was obtained by renal biopsy. It showed a granuloma formation, and was diagnosed as renal sarcoidosis. A high level of interleukin (IL)-6 was detected in his urine. After oral administration of prednisolone, the renal function improved, and the urinary IL-6 level was reduced. These findings suggest that in sarcoidosis associated with renal failure, steroid therapy is effective and that IL-6 plays an important role in the pathogenesis of renal involvement of sarcoidosis.

An autopsy case of cytokeratin 7-positive minute adenocarcinoma of the lung with systemic metastases.

We describe a 60-year-old woman with leg pain. Although metastatic bone tumor and atypical cells mimicking signet-ring cells in the bone marrow picture were observed, systemic survey revealed no primary lesion. The patient died two months after admission from systemic progress of the disease. Autopsy revealed a small focus of adenocarcinoma within the right upper lobe of the lung and systemic metastases without any particular changes in the gastrointestinal tract. The tumor cells of the lung were diffusely positive for cytokeratin 7, whereas cytokeratin 20 immunoreactivity was weak and focal, and that supported the lung origin of the present tumor. Moreover, the tumor cells in the bone marrow showed a similar pattern in immunoreactivity. These findings suggest that cytokeratin 7 and cytokeratin 20 immunoreactivity is helpful for the premortem diagnosis of the metastatic tumor of unknown origin.

A case with small cell carcinoma of the esophagus: measurement of tumor markers, including pro-gastrin-releasing peptide.

Small cell carcinoma of the esophagus is a rare clinical entity and the accumulation of information is necessary to clarify its clinical behavior. We report a 69-year-old Japanese man with this rare disease with systemic metastases, including liver, bone and lymphnodes. The patient was treated with systemic chemotherapy consisting of 300 mg/m2 of carboplatin on day 1, and 80 mg/m2 of etoposide on days 1, 2 and 3. Although transient relief of subjective symptoms was obtained, the disease showed systemic progress, and the patient died on day 25 of chemotherapy. During the clinical course of the disease, serum pro-gastrin-releasing peptide (proGRP) decreased upon systemic chemotherapy from elevated level (54.6 pg/ml) to normal range (19.2 pg/ml). Further study is warranted to examine whether measurement of serum proGRP may yield valuable information on the diagnosis and monitoring activities of esophageal small cell carcinoma.

Interleukin-8 in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis or idiopathic pulmonary fibrosis.

This study was designed to clarify the contribution of IL-8 as a specific neutrophil chemotactic factor in the human respiratory tract in various pulmonary diseases. The neutrophil chemotactic activity (NCA), neutrophil counts and IL-8 concentration in the bronchoalveolar lavage fluid (BALF) obtained from normal volunteers (NV), control patients (CP), patients with diffuse panbronchiolitis (DPB) and patients with idiopathic pulmonary fibrosis (IPF) were examined. Neutrophil counts, NCA and IL-8 concentration in BALF obtained from patients with DPB or IPF was significantly higher than that from NV or CP. The IL-8 concentration correlated with neutrophil count and also correlated with NCA in BALF from patients with IPF, whereas there was no correlation between these factors in BALF from DPB. These results suggest that the contribution of IL-8 to neutrophil accumulation of the lower respiratory tract is different between IPF and DPB.

[A case of rheumatoid lung exacerbated by acetaminophen-induced pneumonitis].

A 57-year-old man was admitted with a high fever, dry cough, severe dyspnea and an interstitial shadow bilaterally on chest roentogenogram. Although his illness was not diagnosed, he was treated with a high dose of methylprednisolone (1 g/day for 3 days) for acute interstitial lung disease. As the 3-day treatment was not effective, high-dose methylprednisolone therapy was repeated. Subsequently, he was treated with prednisolone (60 mg/day), after which his condition improved. After 8 months, the patient caught cold for which he was treated. Subsequently his previous lung disease appeared again. His illness, improved after steroid therapy. The patient had been treated with Shin-Ruru-A tablets during his first admission. A lymphocyte stimulation test for Shin-Ruru-A-Tablet, PL granule, and acetaminophen (which is the common constituent of the former two drugs), was positive. Polyarthralgia, bone lesions joint swelling, and a positive rheumatoid factor test were present on first admission. Therefore, his illness was diagnosed as rheumatoid arthritis (RA). As the interstitial shadow remained after treatment of the lung disease, a thoracoscopic lung biopsy was performed. The specimen revealed an intensive lymphocytic infiltration, perivasculatitis, and thickening of the alveolar septa. These findings corresponded with those of lung disease associated with RA. The results suggest that lung disease associated with collagen vascular diseases may be exacerbated by drug-induced pneumonitis.

The role of cell-associated interleukin-1 in bleomycin-induced pulmonary fibrosis.

The activities of cell-associated IL-1 (IL-1 alpha) and extracellular IL-1 (IL-1 beta) in alveolar macrophages (AM) from rats with bleomycin-induced pulmonary fibrolosis were measured to determine their role in fibroblast growth. AM were obtained on Days 1, 3, 6, 9 and 12 after a intratracheal injection of bleomycin, and the IL-1 activity and fibroblast growth-stimulating activity in fixed AM and AM supernatants were measured. Higher cell-associated IL-1 activity was detected in AM from bleomycin-treated rats than in those of control on Day 1 through 9. But extracellular IL-1 activity in the supernatant of AM from bleomycin-treated rats significantly higher only on Day 1. Expression of IL-1 alpha mRNA in AM from bleomycin-treated rats was significantly higher than that in AM of control, but there was no significant difference in the mRNA levels of IL-1 beta in AM of these two groups. Fixed AM from bleomycin-treated rats caused growth-inhibition of fibroblasts in a density-dependent manner. The inhibitory activity was decreased by pretreatment of fixed AM with anti IL-1 alpha antibody, but not anti IL-1 beta antibody. These results suggest that cell-associated IL-1 (IL-1 alpha) is produced continuously in AM from rats with bleomycin-induced pulmonary fibrosis and may be important in regulation of this disorder by inhibiting fibroblast growth.

Palliative steroid therapy and serum interleukin-6 levels in a patient with lung cancer.

We report a patient with metastatic adenocarcinoma of the lung who had a detectable serum interleukin-6 (IL-6) level. Despite systemic chemotherapy, the tumor progressed, with elevation of serum IL-6 level. Palliative steroid therapy with 20 mg/day of prednisolone resulted in the decline of serum IL-6 level and, simultaneously, improved anorexia and oral intake. Although there was no weight gain or improvement in hypoalbuminemia, these results suggest that steroids may suppress the abnormal production of IL-6 in cancer patients and that this action affects symptoms. Further study is warranted to clarify the role of IL-6 in tumor-related symptoms and the effect of steroid therapy in relation to IL-6 production in cancer patients.

[A study on reduction in care burden of the family caregiver of the bedridden and senile elderly--examination of subjective factors about construction in care burden].

The purpose of this study was to develop a supporting system in the community which reduces care burden of the family caregiver members of bedridden elderly age 75 and over. Preliminary study was carried out in order to find out fundamental elements of care burden. Five families were picked up among the families living in Chuo ward in Tokyo who were provided professional nursing care services at home. A nursing intervention was done through home visits and interviews with caregivers and their subjects who need proper care services. 1. fundamental elements of a caregiver's care burden: a) main elements are health and mental condition of elders, b) influential elements are the function of caregivers, the function of assistant caregivers, the function of professionals and the function of care systems. 2. The line of stress defence: All the functions except that of caregivers were positioned at the line of stress defense, and in our view the caregiver's coping capability would be increased as the line of stress defense functions and, hence, the care burden might be reduced. 3. Assessment of fundamental elements shall be determined from 3 aspects a) health and mental condition of elders, b) accessibility to buffers and their quality and c) capacity and skill of a care giver. In order to reduce the care burden of the family caregiver, it is necessary to assess multilaterally the constituents and/or structures of care in the future, and at the same time the additional functions will be required to furnish information and educate the caregivers on how to utilize various social care services, there by enabling them to cope with psychological stress effectively. These findings suggest that it is also necessary to complete the training of professional concerning feasible means that could promote the caregivers' abilities to cope with the bedridden and senile elderly.

Results of surgical treatment for calcified tuberculous empyema: improved pulmonary function obtained with lung preserving policy.

We treated thirteen cases of calcified tuberculous empyema during the nine years from 1984 to 1992. Six patients having mild symptoms were categorized as Type I, and the remaining seven with severe symptoms as Type II. The patients of Type I were all successfully treated by complete empyemectomy with or without lung resection. All the patients of Type II suffered from major symptoms and were burdened by larger empyema cavities with formation of bronchial fistulas. Five of the latter were successfully treated, but two died, one from MRSA infection and another from intestinal necrosis following omentopexy. Our guide lines for the treatment of tuberculous empyema are: Lung resection must be minimal. Type I patients could be managed by simple empyemectomy with or without minor thoracoplasty. Open thoracostomy prior to the empyemectomy is not necessary. If the patient who belongs to Type II is aged and in a critical state, open thoracostomy must be taken as the first choice. Omentopexy is reliable, but it should be restricted to selected cases. Reasonable dead space and minor air leakage may safely be left behind if the cavity is surrounded by noninfected raw surface of the chest wall and diaphragm. Better quality of life was revealed by exercise test with improved oxygen consumption, compared to the preoperative state.

Effect of alternating combination chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, cisplatin, and etoposide for small cell lung cancer on hematopoietic progenitors in the peripheral blood.

The effects of a combination chemotherapy (CAV-PVP) consisting of cyclophosphamide, doxorubicin, hydrochloride (dox) and vincristine (CAV) alternating with cisplatin and etoposide (PVP) on peripheral blood hematopoietic progenitor cells (PBHPs) were studied in five patients with small cell lung cancer (SCLC). The kinetics of the CFU-GM levels were different during the CAV and PVP phases. None of the five patients displayed a rebound increase in the level of peripheral blood CFU-GM during the CAV phase. In contrast, all five patients displayed a rebound increase in peripheral blood CFU-GM levels during the PVP phase of the alternative combination chemotherapy (3-5 weeks after the initiation of PVP regimen). These findings indicate the optimal timing for leukapheresis to obtain PBHPs in SCLC patients which have been treated with an alternating combination chemotherapy consisting of CAV-PVP.

[Chemical composition of seeds from Cucumeropsis mannii Naudin and their suitability as food]. / Beitrag zur chemischen Zusammensetzung der Samen von Cucumeropsis Mannii Naudin und zu ihrer Eignung als Lebensmittel.

Dehulled seeds from Cucumeropsis Mannii Naudin mainly consist of lipids (40.3%) and proteins (34.5%). Carbohydrates, minerals, and water amount to 16.5, 3.7, and 5.9%, resp. From this composition a caloric value of 2 190 kJ/100 g is calculated. The major component of the oil linoleic acid (57.9%). Short-chain fatty acids are absent. All important macro and micro nutrient elements are present in sufficient amounts for human nutrition. The seeds are rich in vitamin E and in niacin (30.8 mg/100 g and 14.3 mg/100 g. resp.). Consumption of 100 g dehulled seeds covers the daily requirement of essential fatty acids, vitamin E and essential amino acids--methionine excepted. Besides starch (14.3 g/100 g) sucrose (1.14 g/100 g), raffinose (0.42 g/100 g) and stachyose (0.41 g/100 g) as well as traces of glucose and fructose are present. The proteins extracted with various solvents (H2O, 0.1 M KCl-, 0.1 mM K3PO4-, and 0.5% SDS-solution) are studied by amino acid analysis. SDS-electrophoresis and isoelectric focusing. Molecular weights of these proteins are between 5,000 and 80,000 daltons with the fraction between 20,000 and 35,000 predominating. The seeds exhibit weak inhibition of trypsin and do not inhibit alpha-chymotrypsin.