Exploring the size of reference population for expected accuracy of genomic prediction using simulated and real data in Japanese Black cattle.

BACKGROUND: Size of reference population is a crucial factor affecting the accuracy of prediction of the genomic estimated breeding value (GEBV). There are few studies in beef cattle that have compared accuracies achieved using real data to that achieved with simulated data and deterministic predictions. Thus, extent to which traits of interest affect accuracy of genomic prediction in Japanese Black cattle remains obscure. This study aimed to explore the size of reference population for expected accuracy of genomic prediction for simulated and carcass traits in Japanese Black cattle using a large amount of samples. RESULTS: A simulation analysis showed that heritability and size of reference population substantially impacted the accuracy of GEBV, whereas the number of quantitative trait loci did not. The estimated numbers of independent chromosome segments (Me) and the related weighting factor (w) derived from simulation results and a maximum likelihood (ML) approach were 1900-3900 and 1, respectively. The expected accuracy for trait with heritability of 0.1-0.5 fitted well with empirical values when the reference population comprised > 5000 animals. The heritability for carcass traits was estimated to be 0.29-0.41 and the accuracy of GEBVs was relatively consistent with simulation results. When the reference population comprised 7000-11,000 animals, the accuracy of GEBV for carcass traits can range 0.73-0.79, which is comparable to estimated breeding value obtained in the progeny test. CONCLUSION: Our simulation analysis demonstrated that the expected accuracy of GEBV for a polygenic trait with low-to-moderate heritability could be practical in Japanese Black cattle population. For carcass traits, a total of 7000-11,000 animals can be a sufficient size of reference population for genomic prediction.

Preliminary system of rapid analysis of blood retinol level in cattle.

Control of blood retinol levels in cattle during fattening is important in the production of marbled beef. However, it is difficult to easily measure the blood retinol concentration in the field. In this study, we attempted to develop an analysis method that does not require blood cell separation and uses a compact fluorescence analyzer that can be carried around as a preliminary system for measuring blood retinol concentration in the field. This system was used to monitor blood retinol levels in 12 fattening cattle (14 to 27 months old) and demonstrated a strong correlation (r = 0.78) with the results obtained by the standard high-performance liquid chromatography (HPLC) method. Stronger correlations (r = 0.87) were obtained until the cattle were 24 months of age. These results suggest that higher correlations can be expected to be obtained by improving the robustness of the extraction system. Refinements for practical use need to be considered, but whole blood extraction and the vitamin A analyzer that was developed show potential to be used for on-farm monitoring of retinol levels.

[A case of drug-induced pleuritis, possibly due to Hochuekkito].

We report a case of drug-induced pleuritis possibly due to Hochuekkito. Hochuekkito, a Chinese-Japanese herbal medicine, was prescribed for a 33-year-old woman with panic disorder and depressive state. About 10 weeks after the first administration, she was admitted complaining of chest pain and cough. Chest X-ray and computed tomography showed the right pleural effusion. Thoracocentesis revealed eosinophilic pleuritis. Discontinuation of Hochuekkito resulted in improvement of the clinical findings. Based on the clinical course, we considered this case to be Hochuekkito-induced pleuritis.

[A case of pulmonary adenocarcinoma accompanied by minimal change nephrotic syndrome, antiphospholipid syndrome and warm-type autoimmune hemolytic anemia].

A 49-year-old man was urgently admitted due to edema in both leg and left toe pain. A chest radiograph revealed a solitary nodule in the right lung field. Detailed investigations including bronchoscopy and renal biopsy led to a simultaneous diagnosis of clinical stage IIIB pulmonary adenocarcinoma, minimal change nephrotic syndrome, antiphospholipid syndrome, and warm-type autoimmune hemolytic anemia. Prednisolone was administered for nephrotic syndrome, antiphospholipid syndrome and warm-type autoimmune hemolytic anemia, and 6 courses of chemotherapy with 70Gy radio-therapy were performed. The pulmonary nodule significantly decreased in size and the other three autoimmune diseases appeared to be well-controlled. Thirteen months after admission, multiple brain metastases developed along with worsening antiphospholipid syndrome symptoms including lupus anticoagulant. Following whole-brain irradiation, the brain metastases decreased in size and antiphospholipid syndrome symptoms improved. Thirty-nine months after the initial visit, the primary lung cancer, its brain metastasis and the 3 other autoimmune diseases appeared to be well-controlled. The temporal correlation of the lung cancer and the three autoimmune diseases suggests the latter may be paraneoplastic syndrome.

[A case of cryptogenic organizing pneumonia accompanied by large bullae].

A 66-year-old man complaining of fever was given intravenous antibiotic therapy, but he did not improve. After subsequent admission, chest X-ray film and computed tomography scans showed large bullae and consolidation in the right lung field. A transbronchial lung biopsy specimen revealed infiltration of mononuclear cells in alveolar septa and organizing lesions in alveolar ducts. We considered this case to be cryptogenic organizing pneumonia (COP) from its clinical course and pathological findings. Treatment with corticosteroid resulted in disappearance of the large bullae and consolidations. COP accompanied by large bullae is very rare. The large bullae may have been caused by check-valve mechanism.

[Pleurodesis using autologous blood plus OK-432 for intractable spontaneous pneumothorax with high surgical risk].

Air leakage persisted from the lung in three cases of spontaneous pneumothorax. Pleurodesis with autologous blood ended in failure. Autologous blood plus OK-432 was instilled into the thoracic cavity from the chest drainage tube. Air leakage was stopped without serious side effects and the chest tube was removed uneventfully. Although the long-term outcome of this treatment is not known, pleurodesis using autologous blood plus OK-432 may be an effective way of treatment for spontaneous pneumothorax in cases with high surgical risk.

[A case of small cell lung cancer with an initial symptom of breast metastasis].

We report a case of small cell lung cancer with an initial symptom of breast metastasis. A 55-year-old woman was admitted complaining of multiple breast masses. Chest computed tomography (CT) and magnetic resonance imaging (MRI) showed a left hilar mass. Specimens obtained from a breast mass and transbronchial biopsy revealed neoplastic cells suggesting small cell carcinoma Small cell lung cancer with breast metastasis was diagnosed. Systemic chemotherapy resulted in partial remission of the primary lesion and breast metastases.

[Clinical evaluation of bird related hypersensitivity pneumonitis].

We retrospectively evaluated 8 cases of bird related hypersensitivity pneumonitis in Tenri hospital, all of whom underwent surgical lung biopsy. They had a history of contacting with birds and had serological studies using lymphocyte stimulation test to pigeon serum or antibody in serum and bronchoalveolar lavage fluid to pigeon dropping extracts yielded positive results. Computed tomography revealed a radiographic pattern unlike typical UIP. The result of pathological diagnosis of surgical lung biopsy was 'others' or NSIP pattern. Only one case had pathological findings of granuloma. Four cases had an improved or stable course only offer segregation from bird antigens. The other four cases needed corticosteroids and immunosuppressants, and two of the four cases had a progressive course and died of respiratory failure.

Interstitial pulmonary edema revealed by high-resolution CT after relief of acute upper airway obstruction.

We report a case of acute pulmonary edema appearing soon after relief of an acute upper airway obstruction. The patient choked on some pieces of beef during dinner and fainted. He was quickly aided by paramedics and taken to our emergency room with persistent dyspnea and wheezing. His chest radiograph showed bilateral pulmonary edema predominantly distributed in the upper lung field, and high-resolution CT (HRCT) revealed that the pulmonary edema was mainly in the interstitium. The patient recovered uneventfully. HRCT clearly disclosed the characteristics of pulmonary edema of acute upper airway obstruction.

[Autopsy case of pulmonary aspergillosis soon after convalescence from pulmonary tuberculosis].

A 70-year-old man with liver cirrhosis and previous gastrectomy admitted for fever, coughing, and bloody sputum soon after convalescing from pulmonary tuberculosis had a peripheral white blood cell count of 9,900/microL, C-reactive protein of 14.1mg/dL, serum albumin of 2.0g/dL, and serum positive for antiaspergillus and beta-D glucan antibodies. Chest radiography showed thickening of the walls of the large residual cavities with previous tuberculosis lesions and infiltrates around them. On day 2 of hospitalization, Aspergillus fumigatus without other bacillus was detected in sputum culture taken on admission. Despite immediate treatment with intravenous micafungin and oral itraconazole and improved brief initial improvement, his general condition abruptly deteriorated into frequent massive hemoptysis and he developed of shock, respiratory failure, and severe malnutrition, dying 30 days later. Autopsy findings showed pulmonary aspergillosis in and around the large cavities and on the other side of the lungs. Pulmonary aspergillosis without hematological malignanciy and immunosuppression can thus be abruptly severe and fatal due to malnourishment stemming from pre-existing conditions such as chronic hepatitis despite prompt, ordinarily adequate medical treatment.

[Three sisters of pulmonary Mycobacterium avium complex disease].

We reported three sisters of pulmonary Mycobacterium avium complex (MAC) disease. The oldest sister was complaining of bloody sputum, and cultures were positive for M. avium. By monotherapy with clarithromycin, symptom and imaging findings had shown no progression for six years. The second sister was complaining of productive cough, and cultures were positive for M. intracellulare. Her symptom and imaging findings had shown no progression for seven years without any treatment. The third sister had rheumatoid arthritis and diabetes mellitus, and cultures were positive for M. intracellulare. Although she received chemotherapy with rifampicin, clarithromycin, ethambutol, and kanamycin, symptom and imaging findings had progressed gradually. She died of respiratory failure four years later. Autopsy findings revealed no disseminated MAC disease. The results which three cases showed different isolate patterns and clinical courses suggest the importance of underlying anti-mycobacterial immunological impairment and defects of local host defense rather than virulence of infected strains as the pathogenesis of pulmonary MAC disease.

[An adult case of cervico-mediastinal lymph nodes tuberculosis followed by the development of pulmonary lesions during the treatment with antituberculous drugs].

A 27-year-old man was admitted to our hospital due to a painful mass in the right neck and fever. Cervical and superior mediastinal computed tomography showed an enlargement of right supraclavicular lymph node and multiple swollen mediastinal lymph nodes, including low-density areas and contrast medium-enhanced septa and margins. Smears of the pus obtained from right supraclavicular lymph node showed acidfast bacilli identified as Mycobacterium tuberculosis by PCR method. He was treated with antituberculous drugs with INH, RFP, EB, and PZA. PZA was given for initial two months. Six months later, productive cough developed and chest X-ray films showed infiltrative shadow in the right upper lung field. One month after the onset of cough, bronchoscopy revealed a polypoid lesion with a white coating in the right main bronchus. Microscopic examination of the specimen obtained by transbrochial biopsy revealed many epithelioid cell granulomas, consistent with tuberculosis. From these findings, pulmonary lesion was suggested to be due to invasion of the mediastinal lymph node into the bronchus. After one year of antituberculous chemotherapy, the swelling of the cervical-mediastinal lymph nodes was reduced and the abnormal chest X-ray shadows disappeared.

[Case of drug-induced pneumonia possibly due to mefloquine (antimalarial drug)].

A 59-year-old man took mefloquine (antimalarial drug), total dose of 1,000 mg, to prevent malaria before and during traveling to South Africa. Three weeks after the first administration, he was admitted complaining of fever and dyspnea. Chest HRCT showed ground-glass opacities and consolidation in both lung fields. Withdrawal of mefloquine and treatment with corticosteroid resulted in improvement of the clinical findings. From the clinical course, we considered this case to be mefloquine-induced pneumonia. Mefloquine may have caused pulmonary toxicity.

An autopsy case of acute pulmonary toxicity associated with gemcitabine.

Acute respiratory distress syndrome (ARDS) developed following intravenous gemcitabine monotherapy in a 75-year-old man with non-small cell lung cancer. The total dose of gemcitabine was 1,500 mg, and the latent period from starting gemcitabine to pulmonary toxicity was three days. The chest radiographs and high resolution computed tomographic scan revealed bilateral ground-glass opacity. He died on the fourteenth post-chemotherapeutic day due to respiratory failure. Postmortem examination of the lung revealed mixed exudative and fibrotic stages of diffuse alveolar damage. Pulmonary toxicity from gemcitabine can be acute and fatal.

[A case of abrupt pulmonary infection by Rhizopus microsporus var. rhizopodiformis during treatment for bronchial asthma].

We presented a case of pulmonary Rhizops microsporus var. rhizopodiformis infection which developed abruptly during treatment of bronchial asthma by systemic corticosteroids. The patient, an 85 year-old-woman, was given systemic steroid therapy for 15 days. She suddenly became febrile two days after the therapy and was coughing up yellow sputum. Chest X-ray film showed multiple nodules with cavities which became worsened rapidly. A specimen of sputum culture gave a growth of Mucoraceae, which was identified to be Rhizopus microsporus var. rhizopodiformis. She was given amphotericin B and miconazole was added on the basis of MIC value of the strain. Although she improved initially, her clinical course showed neutropenia, pseudomembranous enterocolitis, malnutrition, and then died after about six months. Because the diagnosis of pulmonary mucormycosis is difficult and prognosis is poor, further studies for investigating clinical features would be necessary.

[A case of pulmonaly bulla infection with Mycobacterium fortuitum].

We report a case of bulla infection caused by Mycobacterium fortuitum. The patient was a 66 year-old female associated with interstitial pneumonitis. The chest X-ray film showed cavities with thick walls and niveau formation, which initially suggested pulmonary abscesses. The chest CT scan showed infiltrative shadows surrounding multiple bullae. Smears and cultures of the sputum were repeatedly positive for mycobacteria, which was identified to be M. fortuitum. By chemotherapy with imipenem/cilastatin sodium, clarithromycin, levofloxacin, and minocycline on the basis of susceptibility test, sputum converted to negative within 2 months, abnormal shadows on the roentgenogram and laboratory data showed improvement. There are no signs of recurrence after completion of the treatment for 12 months.

[Clinical evaluation on isolation of Mycobacterium kansasii in our hospital].

MATERIALS AND METHODS: We retrospectively evaluated 49 cases from whom Mycobacterium kansasii (MK) was isolated from 1992 to 2001 in our hospital. RESULTS: The annual numbers of MK patients have increased. One of the clinical characteristics of patients in our cases was relatively low rate of cavitary lesions. In 13 patients who had not fulfilled the diagnostic criteria of MK infection, the clinical disease due to MK did not appear at all during observation period ranging one month to ten years. CONCLUSION: These findings suggest that MK isolation from clinical specimens is not always considered clinically significant, but may be colonization.

[Pulmonary Mycobacterium fortuitum infection with multiple nodular shadows in a healthy man].

We report a case of pulmonary Mycobacterium fortuitum infection with multiple nodular shadows. A 52 year-old male was admitted complaining of fever and chest abnormal shadows. He didn't have pulmonary or systemic underlying diseases. Chest radiograph and computed tomography scan showed multiple nodular shadows in the both lung fields. Isoniazid, rifampicin and ethambutol were administered based on the presumptive diagnosis of tuberculosis. Cultures of the sputum and bronchial washing fluid were repeatedly positive for M. fortuitum, and the case was diagnosed as pulmonary M. fortuitum infection. Although the in vitro susceptibility was resistant to isoniazid, rifampicin and ethambutol, abnormal shadows on the X-ray showed improvement by the combined use of INH, RFP and EB. There are no signs of recurrence after completion of the treatment for 12 months.

[Clinical evaluation on the duration of hospitalization for patients with pulmonary tuberculosis].

In 1996, six-month short course regimen containing PZA was adopted as the standard method of chemotherapy for tuberculosis. According we reevaluated discharge criteria for patients with pulmonary tuberculosis and tried to shorten the duration of hospitalization. We investigated retrospectively the duration of hospitalization for patients with pulmonary tuberculosis who were admitted to the Tenri Hospital. PZA was used for 23.3% of patients who were admitted during 1992 to 1996 (group A, N = 200), and 80.1% of patients who were admitted during 1996 to 2000 (group B, N = 234). The time needed to bacterial negative conversion was significantly shortened from 2.5 months in group A to 1.8 months in group B. The mean duration of hospitalization for patients with pulmonary tuberculosis was significantly shortened from 133.8 days in group A to 63.7 days in group B. Moreover, the mean duration of hospitalization for patients with smear positive pulmonary tuberculosis was significantly shortened from 147.5 days in group A to 73.0 days in group B. There was no significant difference between group A and group B as to the rate of adverse reactions, discontinuation of drug taking and recurrence of the disease. We concluded that the duration of hospitalization for patients with pulmonary tuberculosis could be shortened by applying PZA in the initial phase of tuberculosis chemotherapy.

[Therapeutic drug monitoring of cyclosporine MEPC (Neoral) therapy for interstitial pneumonia].

It is widely recognized that the area under the concentration-time curve (AUC) correlates with the clinical effects of cyclosporine MEPC (Neoral) therapy and adverse reactions to it. In this study, we investigated which single blood-level measurement had correlated best with AUC in interstitial pneumonia therapy. Neoral was prescribed in ten cases of interstitial pneumonia. We measured the concentration during the 4 hours following its administration and calculated AUC0-4 (AUC 0-4 hr). The concentration after 2 hours of administration (C2) correlated best with AUC (r2 = 0.71). This result suggests that C2 monitoring would be a better predictor for AUC than C0 (trough level) monitoring in interstitial pneumonia therapy.