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.

Massive eosinophilic pleural effusion preceding vasculitic symptoms in Churg-Strauss syndrome.

We report a case of Churg-Strauss syndrome (CSS) presenting as a massive pleural effusion. A 52-year-old asthmatic Japanese woman presented with progressive dyspnea caused by an eosinophilic pleural effusion (EPE). She also had chronic sinusitis, skin lesions and blood eosinophilia, but no antineutrophil cytoplasmic antibodies. Skin biopsy and the late onset of mononeuritis multiplex led to the diagnosis of CSS. The pleural effusion resolved soon after corticosteroid treatment was started. CSS is rare as a cause of EPE, but should be included in the differential diagnosis of EPE in asthmatic patients. This is the first report showing that EPE can precede other vasculitic symptoms in CSS.

Pulmonary thrombosis with transient antiphospholipid syndrome after mononucleosis-like illness.

Antiphospholipid antibodies (aPL) have been reported to occur in numerous viral infections. We report a 24-year-old Japanese woman, who developed multiple venous thrombosis associated with the elevation of anticardiolipin IgM after acute viral infection presenting a mononucleosis-like illness. Two months later, aPL and thromboses disappeared. In this case both parvovirus B19 and cytomegalovirus antibodies IgM were elevated, which indicated the possibility of cross-reaction.

[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.

[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.

[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.

[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.

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.

[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.

[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.

[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.

Alendronate reduced vertebral fracture risk in postmenopausal Japanese women with osteoporosis: a 3-year follow-up study.

The risk-reducing effect of alendronate on vertebral fractures has been consistently reported. In a 2-year, randomized, double-blind, active drug-controlled (1 microg alfacalcidol) double-dummy study, we also reported that alendronate (5.0 mg) had a fracture-reducing effect in Japanese patients with preexisting vertebral fractures. The present report describes the risk-reducing effect of alendronate (5.0 mg) for 3 years in postmenopausal osteoporotic patients. The 3-year treatment period consisted of the original 2-year double-blind study followed by a 1-year extension. A total of 170 postmenopausal female patients were involved in the third year; 90 received alendronate and 80 received alfacalcidol. Both efficacy and safety were analyzed in these 170 patients. Vertebral fracture was determined by quantitative morphometry, and vertebral bone mineral density (BMD) was measured by the DXA method (dual-energy X-ray absorptiometry). The primary efficacy endpoint was the incidence of vertebral fracture, excluding fracture cases that occurred in the first 6 months after treatment initiation. The cumulative incidence of vertebral fracture at 3 years was 7.8% (7/90) in the alendronate group and 18.8% (15/80) in the alfacalcidol group, indicating a significantly reduced risk of fractures in the alendronate group (relative risk = 0.41, 95% CI = 0.18-0.97). Lumbar spine BMD increased by 9.2% in the alendronate group (n = 26) and by 1.4% in the alfacalcidol group (n = 22) at 3 years. The safety profile of alendronate during 3 years of treatment was similar to that of alfacalcidol. The present study thus demonstrated that treatment with alendronate 5.0 mg for 3 years increased vertebral BMD and reduced the risk of vertebral fractures in Japanese, postmenopausal women with osteoporosis.

A comparison of incidences of vertebral fracture in Japanese patients with involutional osteoporosis treated with risedronate and etidronate: a randomized, double-masked trial.

To demonstrate the clinical benefit of risedronate at 2.5 mg daily in the treatment of involutional osteoporosis, the effect of risedronate on incidence of vertebral fracture was compared with that of etidronate. A total of 547 patients with one to four vertebral fractures were randomized to receive either treatment with 2.5 mg/day of risedronate or intermittent treatment (treatment of 2 weeks and off period of 10 weeks) with 200 mg/day of etidronate for 96 weeks in a double-masked fashion. All patients received 200 mg calcium supplement daily. Lateral and anteroposterior thoracic and lumbar spine radiographs were obtained at baseline and at 24, 48, 72, and 96 weeks. Cumulative incidence rates of patients who had at least one new or worsening vertebral fracture during the 96-week period were 12.3% for risedronate and 14.2% for etidronate, and it was verified that the fracture prevention effect of risedronate was not inferior to that of etidronate. The incidence rates of fracture during the initial 24-week period were 8.8% for risedronate and 6.0% for etidronate, but the cumulative incidence rate of fracture from 24 to 96 weeks was lower in the risedronate group (3.9%) as compared to the etidronate group (8.7%). Height loss was significantly less in the risedronate group (-0.28 cm) than in the etidronate group (-0.70 cm) after 96 weeks. Decreases in bone resorption markers including urinary total deoxypyridinoline and NTX were significantly greater in the risedronate group than in the etidronate group throughout the treatment period. An improvement of patient QOL was observed in both groups. No significant difference in the incidence of adverse events was observed between the two treatments. Daily oral risedronate (2.5 mg) was shown to provide an effective therapy for involutional osteoporosis in Japanese patients with good tolerability.