Biomedical subjects
Junichi Nakamura
Publications and source records attributed to Junichi Nakamura.
Changes in serum KL-6 after intravenous fosfomycin administration in idiopathic interstitial pneumonia.
Changes in serum KL-6 levels after intravenous fosfomycin (FOM) administration in idiopathic interstitial pneumonia (IIP) were studied. Seventeen patients who were diagnosed with usual interstitial pneumonia by surgical lung biopsy were selected as subjects. In these patients, FOM was administered intravenously, at a dose of 2 g twice daily, for 14 days, and serum KL-6 was determined before and after its administration. FOM administration resulted in a reduction of serum KL-6 in all 17 patients (1273 +/- 132 U/ml [mean +/- SEM] to 1023 +/- 101 U/ml; P < 0.01). FOM may reduce serum KL-6 in IIP and may be an appropriate therapeutic drug for this condition.
Clinical features of Q fever pneumonia.
The aim of the study was to assess the clinical features of Q fever pneumonia in Japan. Four cases of Q fever pneumonia (a female aged 21 and males aged 53, 74 and 87 years) who were diagnosed using the PanBio ELISA test kit, were assessed and their clinical features are described. The frequency of Q fever pneumonia among our cases of community-acquired pneumonia was 1.4% (4/284). A 21-year-old female had a typical case of the disease with (i) a history of owning a cat, (ii) onset with fever and dry cough, (iii) multiple soft infiltrative shadows on CXR, (iv) a normal white blood cell count, and (v) good response to clarithromycin. The pneumonias in the other three cases were considered mixed infections with bacteria such as Streptococcus pneumoniae and Haemophilus influenzae. Their clinical features included the following: (i) an elderly person with an underlying disease, (ii) onset with fever and purulent sputum, (iii) coarse crackles on auscultation, (iv) infiltrative shadows and pleural effusion on CXR, (v) increased white blood cells with elevated BUN and hyponatraemia, and (vi) modest responses to combined therapy with carbapenem and minocycline. Our observations suggest that two types of pneumonia caused by Coxiella burnetti exist; one with the usual features of atypical pneumonia, and the other presenting with the clinical features of bacterial pneumonia in the elderly due to mixed bacterial infection.
[A case of poorly differentiated lung adenocarcinoma showing air-space consolidation caused by aerogenic metastasis].
A 78-year-old woman was admitted to our hospital because of dyspnea. A chest radiograph and a computed tomogram on admission showed air-space consolidation in the left upper lung field, and so pneumonia was diagnosed. Although antibiotics were administered, the air-space consolidation did not improve. A transbronchial lung biopsy was performed, yielding a pathologic diagnosis of poorly differentiated lung adenocarcinoma. Despite combination chemotherapy with docetaxel and UFT, the air-space consolidation expanded, and the patient finally died of respiratory failure 3 months after diagnosis. Autopsy revealed air-space consolidation due to poorly differentiated lung adenocarcinoma, with large atypical cells diffusely floating in the alveolar spaces. It has been recognized that bronchiolo-alveolar carcinoma and well-differentiated lung adenocarcinoma present with air-space consolidation, reflecting the cancer cells lining the alveolar walls. However, in this case, the air-space consolidation was due to cancer cells diffusely floating in the alveolar spaces in aerogenic metastasis. It was considered that this is a rare case, which presented with a very interesting development pattern.
[A case of allergic granulomatosis and angiitis (Churg-Strauss syndrome) in a 15-year-old girl].
A 15-year-old girl with a 6-month history of bronchial asthma was admitted to our hospital because of fever, dyspnea, weight loss, dysesthesia, muscle weakness, gait disturbance and purpuric rash. In addition, leukocytosis, hypereosinophilia and elevation of CRP were observed. Chest radiograph and computed tomography on admission showed non-segmental patchy air-space consolidation in both lung fields. Skin biopsy was performed and the pathologic diagnosis was necrotizing arteritis with eosinophilic infiltration. Transbronchial lung biopsy revealed eosinophilic pneumonia. From the clinical course, laboratory data and pathologic findings, the diagnosis of allergic granulomatosis and angiitis (Churg-Strauss syndrome) was made. Following the skin and lung biopsies, intravenous pulse corticosteroid and oral prednisolone treatment was started and her clinical findings improved. Angiitis with allergic granulomatosis is a vasculitis that is found in adults. This is an extremely rare and interesting case of angiitis with allergic granulomatosis in childhood.
Health-related quality of life in outpatients of a psychosomatic medicine clinic: a pilot survey in Japan.
The objective of this study is to clarify the difference of health-related quality of life (HRQoL) profiles by disease category with the SF-36 questionnaires, and to examine the possibility of application for a longitudinal study. A number of subjects was 536, specifically 127 men and 409 women. For all of the eight domains, Cronbach's alpha exceeded 0.7. Categories in which all of the domains were approximately equal to the national standard included hypertension, neck and shoulders syndrome, diabetes, hyperlipidemia and cardiac disease. Bodily pain was especially lower in gastrointestinal disorder, spondylopathy and hemopathy. Patients with mental disorder had lower scores in all domains. Categories in which 5-7 of the eight domains had lower scores included arthropathy, asthma, chronic hepatitis, autonomic imbalance, 'ovariopathy and hysteropathy' and chronic rheumatism. No significant change was found between the first and second scores in hypertension as a representative of the high HRQoL categories. In mental disorder as a representative of the low HRQoL categories, however, five of the eight domains increased significantly. We concluded that a target disease should be chosen among subjects with low HRQoL scores before an intervention to assess its effectiveness. Or subjects with high HRQoL scores can be examined to determine whether they keep the same level of HRQoL.
Status of p53 phosphorylation and function in sensitive and resistant human cancer models exposed to platinum-based DNA damaging agents.
PURPOSE: Resistance to chemotherapeutic drugs is a hallmark of many human cancers, which can occur independent of p53 gene status; however, the presence of wild-type p53 in chemorefractory tumors confers greater resistance to cisplatin, but such tumors do not display complete cross-resistance to the platinum analog (1R,2R-diaminocyclohexane)(trans-diacetato)(dichloro)platinumIV (DACH-Ac-Pt). In this article we examine DNA damage-induced phosphorylation of p53 and downstream p53-dependent transactivation events in cisplatin-sensitive and cisplatin-resistant human cancer cell lines possessing wild-type p53. METHODS: Western-blot analysis was utilized to study the effect of cisplatin and the analog on p53 phosphorylation and p53-dependent target genes. RESULTS: In response to CDDP and DACH-Ac-Pt, both CDDP-sensitive and CDDP-resistant models demonstrated time- and dose-dependent inductions of total p53 protein and an increase in Ser-15 phosphorylation, which was more pronounced with CDDP. Although phosphorylation of p53 at Ser-392 was also observed in CDDP-treated sensitive and resistant cells, it was weak or absent in response to DACH-Ac-Pt. Lack of Ser-392 phosphorylation by DACH-Ac-Pt, however, did not affect the induction of p21(WAF1/CIP1) or Mdm2. Similarly, inductions of p21(WAF1/CIP1) and Mdm2 were observed in sensitive cells exposed to cisplatin. In marked contrast, cisplatin-mediated induction of p21(WAF1/CIP1) was minimal or absent in resistant cells, but that of Mdm2 was unaffected. Wortmannin, a PI3-kinase (PI3-K) inhibitor, caused a dose-dependent inhibition of total p53 accumulation, Ser-15 phosphorylation and p21(WAF1/CIP1) transactivation in response to both CDDP and DACH-Ac-Pt, indicating that members of the PI3-K family are involved in phosphorylation of p53 and that transactivation of p21(WAF1/CIP1) is p53 dependent. CONCLUSION: These studies demonstrate that cisplatin and DACH-Ac-Pt differentially phosphorylate p53 through independent DNA damage-induced pathways, and that the kinase-mediated phosphorylation of p53 at Ser-15 or Ser-392 is unaltered in resistance. Moreover, the phosphorylation status of Ser-392 on its own does not appear to correlate with p21(WAF1/CIP1) or Mdm2 induction in these studies; however, a lack of increase in p21(WAF1/CIP1) by cisplatin, but not DACH-Ac-Pt, provides a correlation with resistance and its circumvention, and implicates the role for cyclin-dependent kinase inhibitor in the differential cytotoxic effects of the two platinum agents against resistant cells.
Clinical effect of ampicillin with beta-lactamase inhibitor (sulbactam/ampicillin) on community-acquired pneumonia in the elderly.
Sulbactam/ampicillin (SBT/ABPC) was administered to 83 patients aged over 75 years with community-acquired bacterial pneumonia (mild, n = 43; moderate, n = 40), and its clinical effect was reviewed. It was effective in 37 of the 43 patients with mild disease (efficacy rate, 86.0%), in 27 of the 40 patients with moderate disease (efficacy rate, 67.5%), and overall in 64 of the 83 patients (efficacy rate, 77.1%). Side effects included drug eruption in 1 patient (1.2%) and abnormal laboratory findings in 11 (13.3%), all of which were mild. Based on the above, SBT/ABPC may be recommended as the first-choice drug for community-acquired bacterial pneumonia in the elderly.
[Q fever in acute exacerbation of bronchial asthma].
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[Incidence of Q fever pneumonia in community-acquired pneumonia around Okayama City--the second report].
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[Clinical features of Q fever pneumonia].
We report four cases of Q fever pneumonia diagnosed using PanBio Coxilla burnetii ELISA. The patients, a 21-year-old woman, a 53-year-old man, a 74-year-old man and a 87-year-old man, were among 284 with community-acquired pneumonia who were treated as inpatients from March 2001 till March 2003. The frequency of Q fever pneumonia in community-acquired pneumonia was 1.4%. The 21-year-old woman was a typical case of Q fever pneumonia, since her clinical features showed 1. the breeding of cats, 2. development from a fever and non-productive caught in March, 3. multiple soft consolidations in the chest radiograph, 4. normal WBC count, 5. cure by administration of clarithromycin. The pneumonias of the other 3 cases were considered to be mixed infections, with bacteria such as Streptococcus pneumoniae and Haemophilus influenzae. Their clinical features were 1. elderly male patients with underlying diseases, 2. development from fever and cough with purulent sputum in winter, 3. coarse crackle on auscultation, 4. consolidation with pleural effusion in chest radiograph, 5. leukocytosis, elevation of BUN, hyponatremia, 6. a few cases with unfavorable prognoses despite medication with carbapenem and minocycline. These findings suggested that two types of pneumonia exist; one with the usual features of atypical pneumonia, and the other presenting the clinical features of bacterial pneumonia of the elderly due to a mixed infection including C. burnetti.
The interaction of 2-phenylbenzimidazole compounds with DNA: the influence of terminal substituents.
We have studied the influence of terminal substituents, amidinium group and N-methylpiperazine ring, of 2-phenylbenzimidazole compounds (1-6; Figure 1) on their DNA-binding modes. Experimental results reveal that 1-3 are accepted in intercalation pockets owing to structural flexibility of the N-methylpiperazine ring, while 4-6 bind to the groove of DNA because of steric hindrance between the amidinium group and the DNA phosphate-sugar backbone.
[Diagnosis of bacterial pneumonia by serum beta-globulin demarcation].
We studied whether the consolidation whose serum beta-globulin demarcation showed more than 12% was bacterial pneumonia or not. The materials were the patients with fever (> or = 37 degrees C) and the consolidation on chest-X ray film, the value of serum beta-globulin demarcation was more than 12% from 1995 to 2000. There were 5 cases with drug-induced pneumonitis, 5 cases with BOOP, 2 cases with eosinophilic pneumonia, 1 case with lung cancer (adenocarcinoma), and 1 case with interstitial pneumonia with dermatomyositis. No one had bacterial pneumonia. These results suggested the consolidation with fever whose serum beta-globulin demarcation showed more than 12% was not bacterial pneumonia.
[Incidence of Q fever pneumonia in community acquired pneumonia around Okayama City].
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Adrenocorticotropin-producing pituitary carcinoma with metastasis to the liver in a patient with Cushing's disease.
A 61-year-old woman who had a nonfunctioning pituitary tumor removed was later found to have a pituitary carcinoma with metastasis to the liver that produced adrenocorticotropic hormone (ACTH), causing Cushing's disease. Despite the second removal of the pituitary tumor, Cushing's disease persisted. Endocrinologic examination demonstrated marked elevation of plasma ACTH, beta-endorphin, and serum cortisol concentrations, which were not suppressed by low- or high-dose dexamethasone administration. A computed tomographic scan of the abdomen revealed a solitary hypodense area in the liver consistent with a metastatic lesion. Immediately after resection of the liver tumor, plasma ACTH concentrations fell to normal range. Such a decline in ACTH secretion was not observed even after the pituitary tumor was removed. Histologic characteristics of both the pituitary and liver tumors were similar. The immunohistochemical study using anti-ACTH antibody showed similar ACTH-positive cells in the pituitary and liver tumors. Based on these findings, the patient was diagnosed as having liver metastasis of ACTH-secreting pituitary carcinoma. This is the first case report in which a metastatic liver tumor of a pituitary carcinoma caused ACTH.