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The interaction of Aspergillus fumigatus with human bronchial mucosa in an organ culture model, with an air-mucosal interface, was studied. A. fumigatus conidia were inoculated onto the organ culture tissues and incubated for 24 h. At each time point (1, 6, 12, 18 and 24 h), after the measurement of ciliary beat frequency (CBF) of bronchial epithelial cells, adherence and invasion of the epithelium by A. fumigatus conidia (and hyphae), as well as structural changes of the epithelium, were investigated by scanning and transmission electron microscopy. This study demonstrated that A. fumigatus caused damage to the bronchial epithelium that was associated with CBF slowing. In addition, the study demonstrated that some of the conidia of A. fumigatus were internalized within ciliated and non-ciliated epithelial cells, some conidia were located within the intercellular spaces of the epithelium, and that hyphae penetrated through both intercellular and intracellular spaces of the epithelium. These findings suggest there might be at least three pathways by which Aspergillus invades the bronchial mucosa: (1) penetration of hyphae through the intercellular spaces in the epithelium; (2) direct penetration of hyphae through epithelial cells; and (3) internalization of conidia within epithelial cells. [ABSTRACT FROM AUTHOR]

To investigate the effects of scattered radiation when a thin titanium plate (thickness, 0.05 cm) used for skull fixation in cerebral nerve surgery is irradiated by a 4-MV photon beam. We investigated the dose distribution of radiation inside a phantom that simulates a human head fitted with a thin titanium plate used for post-surgery skull fixation and compared the distribution data measured using detectors, obtained by Monte Carlo (MC) simulations, and calculated using a radiation treatment planning system (TPS). Simulations were shown to accurately represent measured values. The effects of scattered radiation produced by high-Z materials such as titanium are not sufficiently considered currently in TPS dose calculations. Our comparisons show that the dose distribution is affected by scattered radiation around a thin high-Z material. The depth dose is measured and calculated along the central beam axis inside a water phantom with thin titanium plates at various depths. The maximum relative differences between simulation and TPS results on the entrance and exit sides of the plate were 23.1% and − 12.7%, respectively. However, the depth doses do not change in regions deeper than the plate in water. Although titanium is a high-Z material, if the titanium plate used for skull fixation in cerebral nerve surgery is thin, there is a slight change in the dose distribution in regions away from the plate. In addition, we investigated the effects of variation of photon energies, sizes of radiation field and thickness of the plate. When the target to be irradiated is far from the thin titanium plate, the dose differs little from what it would be in the absence of a plate, though the dose escalation existed in front of the metal plate.

Objective: Complete congenital heart block (CHB) due to anti-Ro/La antibodies in pregnancy can lead to adverse fetal outcomes and neonatal death. National and international guidelines do not recommend specific treatment for women identified with anti-Ro antibodies while pregnant., Design: Systematic review of studies of pregnant women with anti-Ro/La antibodies undertaking treatment(s) to prevent CHB. Studies solely focused on treating developing or established CHB were excluded., Main Outcome Measure: CHB incidence., Results: Of 1049 articles, 20 studies were eligible, of which 13 were retrospective. Sixteen studies contained usable data comparing various treatments (seven hydroxychloroquine (HCQ), six corticosteroids, two intravenous immunoglobulin (IVIG) and one each on combined HCQ and corticosteroids and plasmapheresis), including 2134 women and 2915 pregnancies. Meta-analysis was not possible due to heterogeneity. HCQ as primary prophylaxis showed protective effect on CHB incidence in four of five studies, whereas for preventing recurrence, only one study had a comparator arm, which showed a protective effect. Corticosteroids showed protective effect on CHB incidence as primary prophylaxis in two of three studies, whereas in recurrence, only one study showed protective effect. The IVIG study with a comparator showed no protective effect on CHB recurrence. Two studies (IVIG and plasmapheresis) had no comparator. The long-term toxicity of treatments was poorly investigated., Conclusion: HCQ showed the most evidence among various treatment options to prevent CHB in babies of women with anti-Ro/La antibodies. However, included studies had high risk of bias and imprecision. Future studies should be prospective, compare existing treatments and capture adverse effects.PROSPERO registration number CRD42023492934., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Purpose: The number of frozen-thawed embryo transfers (FETs) has recently increased, and FET must be completed in the ovulatory (NC-FET) or programmed hormone replacement cycle (HRC-FET). However, the relationship between FET and abnormal placentation is unclear. This study aimed to determine whether the two distinct endometrial preparation protocols affect the incidence of several pathologic conditions caused by abnormal placentation, such as placenta with velamentous umbilical cord insertion (VCI), hypertensive disorders of pregnancy (HDP), and placenta accreta spectrum (PAS)., Methods: For this retrospective cohort study, the medical records of 1,161 singleton term FET-conceived and -delivered cases were reviewed from January 2016 to July 2024. The study population was categorized into HRC-FET (Group A: n = 846) and NC-FET (Group B: n = 315) cases. After adjusting for confounding factors, the odds ratios (ORs) of the investigated targeted variables in Group A compared to Group B were calculated using multivariate logistic regression., Results: The incidence of VCI and PAS in Groups A and B was 7.0% and 2.5% for VCI and 5.1% and 1.0% for PAS, respectively, with a significant difference (P < 0.01). The adjusted ORs for VCI, PAS, and HDP in Group A compared to those in Group B were 3.07 (P < 0.01), 5.73 (P < 0.01), and 1.24 (P = 0.42), respectively., Conclusion: Pregnancies achieved through HRC-FET have higher risks of developing abnormal placentation (i.e., VCI and PAS) than those achieved through NC-FET. These pregnancies are high risk and should be managed carefully for a healthy perinatal course., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: The study protocols conformed to the provisions of the Declaration of Helsinki (revised in Tokyo, 2004) and were approved by the Kubonoya Women’s Hospital Ethics Committee and Review Board, which approved the use of an electronic medical record database for this clinical study (approval no. 2024–1). Informed consent: The requirement to obtain informed consent from the patients involved was waived because of the study’s observational retrospective cohort design. Consent to publish: Not applicable., (© 2025. The Author(s).)

Objective: Stanford type A acute aortic dissection (AAD) is associated with carotid artery dissections (CADs). We report two cases of carotid artery stenting (CAS) for symptomatic CAD after ascending aortic replacement (AAR) for AAD., Case Presentation: Case 1: A 51-year-old man with AAD was transferred to our institute. He had no notable paralysis symptoms on initial presentation. However, after AAR for AAD was performed, left paralysis developed within a few hours. Emergency angiography revealed right CAD and pseudo-occlusion. CAS was performed successfully using intravascular ultrasound (IVUS). He was transferred to a rehabilitation hospital with a modified Rankin Scale (mRS) score of 2.Case 2: A 55-year-old man underwent AAR for AAD, but asymptomatic left CAD remained. Two weeks after the operation, he presented with slight signs of aphasia. Aspirin was prescribed and follow-up was performed, but his symptoms did not improve. He underwent magnetic resonance imaging in our department, which revealed acute cerebral infarction on the left pars opercularis and an artery-to-artery embolism from CAD. CAS was performed via the retrograde approach with direct puncture of the normal left common carotid artery using IVUS. He was discharged with no complications and a mRS score of 1., Conclusion: IVUS can be useful for CAS to confirm the true lumen and extension of long CAD lesions developing from AAD., Competing Interests: The authors declare no conflict of interest., (©2021 The Japanese Society for Neuroendovascular Therapy.)

1α-Hydroxylation of 25-hydroxyvitamin D3 is believed to be essential for its biological effects. In this study, we evaluated the biological activity of 25(OH)D3 itself comparing with the effect of cell-derived 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). First, we measured the cell-derived 1α,25(OH)2D3 level in immortalized human prostate cell (PZ-HPV-7) using [(3)H]-25(OH)D3. The effects of the cell-derived 1α,25(OH)2D3 on vitamin D3 24-hydroxylase (CYP24A1) mRNA level and the cell growth inhibition were significantly lower than the effects of 25(OH)D3 itself added to cell culture. 25-Hydroxyvitamin D3 1α-hydroxylase (CYP27B1) gene knockdown had no significant effects on the 25(OH)D3-dependent effects, whereas vitamin D receptor (VDR) gene knockdown resulted in a significant decrease in the 25(OH)D3-dependent effects. These results strongly suggest that 25(OH)D3 can directly bind to VDR and exerts its biological functions. DNA microarray and real-time RT-PCR analyses suggest that semaphorin 3B, cystatin E/M, and cystatin D may be involved in the antiproliferative effect of 25(OH)D3., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

According to the prevailing paradigm, 1α-hydroxylation of 25-hydroxyvitamin D(3) (25(OH)D(3)) and its analogs is a pre-requisite step for their biological effects. We previously reported that 25-hydroxy-19-nor-vitamin D(3) (25(OH)-19-nor-D(3)) had anti-proliferative activity in a cell line, PZ-HPV-7, which was derived from human non-cancerous prostate tissue, and suggested that 25(OH)-19-nor-D(3) acted after 1α-hydroxylation by vitamin D 1α-hydroxylase (CYP27B1). However, metabolic studies of 25(OH)-19-nor-D(3) using recombinant CYP27B1 revealed that 25(OH)-19-nor-D(3) was rarely subjected to 1α-hydroxylation. Therefore, in this report, we attempted to clarify the mechanism of 25(OH)-19-nor-D(3) action in intact cells using PZ-HPV-7 prostate cells. After incubating the cells with 25(OH)-19-nor-D(3), eight metabolites of 24-hydroxylase (CYP24A1) were detected, whereas no products of CYP27B1 including 1α,25-dihydroxy-19-nor-vitamin D(3) (1α,25(OH)(2)-19-nor-D(3)) were found. Furthermore, the time-dependent nuclear translocation of vitamin D receptor (VDR) and the subsequent transactivation of cyp24A1 gene in the presence of 25(OH)-19-nor-D(3) were almost identical as those induced by 1α,25(OH)(2)-19-nor-D(3). These results strongly suggest that 25(OH)-19-nor-D(3) directly binds to VDR as a ligand and transports VDR into the nucleus to induce transcription of cyp24A1 gene. In addition, knock down of cyp27B1 gene did not affect the anti-proliferative activity of 25(OH)-19-nor-D(3), whereas knock down of VDR attenuated the inhibitory effect. Thus, our results clearly demonstrate that the anti-proliferative activity of 25(OH)-19-nor-D(3) is VDR dependent but 1α-hydroxylation independent, suggesting that 25(OH)D(3) analogs such as 25(OH)-19-nor-D(3) could be attractive candidates for anticancer therapy.

Image-guided radiation therapy using a gold marker-based tumor tracking technique provides precise patient setup and monitoring. However, the marker consists of high-Z material, and the resulting scattered rays tend to have adverse effects on the dose distribution of radiotherapy. The purpose of this study was to evaluate the dosimetric perturbation due to the use of a gold marker for radiotherapy in the lungs. The relative dose distributions were compared with film measurement, Monte Carlo simulation, and XiO calculation with the multi grid superposition algorithm using two types of virtual lung phantoms, which were composed of tough water phantoms, tough lung phantoms, cork boards, and a 2.0-mm-diameter gold ball. No dose increase and decrease in the vicinity of the gold ball was seen in the XiO calculations, although it was seen in the film measurements and the Monte Carlo simulation. The dose perturbation due to a gold marker cannot be evaluated using XiO calculation with the superposition algorithm when the tumor is near a gold marker (especially within 0.5 cm). To rule out the presence of such dose perturbations due to a gold marker, the distance between the gold marker and the tumor must therefore be greater than 0.5 cm.

The purpose of present study was to examine spleen-selective gene transfer following the administration of naked plasmid DNA (pDNA) onto the spleen surface in mice. Gene expression in the spleen and other tissues was evaluated based on firefly luciferase activity. Six hours after spleen surface instillation of naked pDNA, high gene expression in the spleen was observed. On the contrary, intravenous and intraperitoneal administration of naked pDNA resulted in no detectable gene expression. After instilling naked pDNA onto the spleen surface, gene expression in the spleen was significantly higher than those in other tissues. Six hours after instillation of naked pDNA onto the spleen surface, gene expression in the spleen reached the peak value, and thereafter decreased gradually. By utilizing a glass-made diffusion cell that is able to limit the contact dimension between the spleen surface and naked pDNA solution administered, site-specific gene expression in the spleen was found. This novel gene transfer method is expected to be a safe and effective strategy for DNA vaccine against serious infectious diseases and cancers.

Objective: Bronchopleural fistula is a critical complication that may occur after pulmonary resection. Early closure of the fistula is required to prevent thoracic empyema or aspiration pneumonia. We have designed a novel procedure for bronchoscopic occlusion of the fistula with a collagen screw plug and assessed its feasibility in an experimental animal model., Methods: Adult beagle dogs underwent right or left pneumonectomy, and the bronchial stump was closed with the Sweet method. A silicone bar (2 mm in diameter) was then placed in the middle of the bronchial stump. Seven days after the operation, the silicone bar was removed bronchoscopically, and fistula formation was confirmed. A screw-shaped 2% collagen screw plug (20 mm long and 3 mm in diameter) was mounted at the end of a modified endoscopic cannula and then inserted into the fistula. Autologous platelet-rich plasma was then soaked onto the inserted plug., Results: Nine of 10 beagle dogs with bronchopleural fistula were treated successfully by plug occlusion. One dog died of pneumothorax caused by dislocation of the plug. Pathologic examination revealed that the collagen sponge had been replaced by fibrous tissue and that the fistula was covered with normal epithelium. Although soaking with platelet-rich plasma made the plug airtight immediately, the use of platelet-rich plasma seemed to make no distinct difference with respect to the treatment result or pathologic findings., Conclusion: Bronchoscopic occlusion with a collagen screw plug is a promising option for treatment of small bronchopleural fistulas after pulmonary surgery.

In this study, twelve cases of CEP were followed for a mean period of 10.9 years (range 9.3-12.9 years) at National Himeji Hospital. Of the five women and seven men examined, two patients possessed preexisting asthma and one developed asthma during the course of CEP disease. None of the patients exhibited any symptoms of allergic rhinitis. All had dramatic responses to corticosteroid therapy without developing extrathoracic manifestations. During the course of CEP, one patient died from acute myocardial infarction. Relapses, which occurred in six patients, responded as well to the treatment as in the original episode. One patient continued long-term oral corticosteroids (5 mg/day) and steroid inhalants (800 micrograms/day) as treatment for asthma. Another was administered steroid inhalants (800 micrograms/day) to treat both asthma and relapsing CEP; two additional patients received 800-600 micrograms/day to prevent relapse. These data indicate that, with proper treatment, the long-term prognosis for patients with CEP is excellent.

The present study has undertaken the liver- and lobe-selective gene transfections following the instillation of plasmid DNA (pDNA) to the liver surface in mice. The luciferase levels produced in the applied (left) liver lobe at 6 h after liver surface instillation of pDNA were significantly higher than those produced in the other tissues assayed, and ranged from 8.5-fold higher in other liver lobes to 320-fold higher in other tissues. After small intestine surface instillation of pDNA, the gene expression was a little detected in the tissues assayed. Following liver surface instillation of pDNA at a time from 2 to 48 h or at a volume from 15 to 120 microl, the gene expressions of the applied liver lobe were always significantly higher than those of other liver lobes and other tissues. We demonstrated the novel liver- and lobe-selective gene transfection utilizing the instillation to the liver surface.

An 84-year-old man was referred to our hospital because of fever, cough, and hemoptysis. The patient had acute respiratory failure (PaO2 < 40 mmHg) on admission, with diffuse interstitial infiltration and bilateral pleural effusion. The bronchoalveolar lavage fluid was bloody, and contained a high percentage of eosinophils (32%). A diagnosis of acute eosinophilic pneumonia was established, and the patient made a rapid recovery after corticosteroids were administered. When the DLST (drug lymphocyte stimulation test) was performed after the corticosteroid therapy was stopped, it was positive for serrapeptase, which had been prescribed for chronic cystitis for 3 months before the onset of the pneumonia. This was a case of drug (serrapeptase)-induced pneumonitis manifesting as acute eosinophilic pneumonia.

A 30-year-old woman was admitted to our hospital because of productive cough, wheezing, and the disclosure of abnormal shadows on chest X-ray films. The patient was given a diagnosis of allergic bronchopulmonary aspergillosis (ABPA) based on eight findings: asthma, eosinophilia, elevated serum IgE concentrations, immediate skin reactivity to Aspergillus antigen, the presence of precipitating antibodies against Aspergillus antigen, lung infiltration, central bronchiectasis, and repeated culture of Aspergillus fumigatus in sputum. Because she refused steroids, we administered erythromycin. The volume of her sputum subsequently decreased, her symptoms were brought under control, and her serum IgE fell, but the lung infiltrates did not clear. Discontinuation of erythromycin resulted in exacerbation of the patient's asthmatic symptoms, with high fever, increased sputum volume and IgE levels, and worsening lung infiltrates. These symptoms responded well to oral prednisolone medication, but sputum culture was still positive for Aspergillus fumigatus. Following discontinuation of prednisolone, the patient was treated with erythromycin, to which oral fluconazole was added for 16 months. Subsequent sputum cultures were negative for Aspergillus fumigatus, and for 7 years thereafter the patient remained in remission. Erythromycin and anti-fungal drugs may be worth trying in cases of allergic bronchopulmonary aspergillosis.

We analyzed retrospectively the clinical data of 12 patients diagnosed as pulmonary tuberculosis after admission to the National Himeji Hospital during the past 5 years. Ten out of 12 patients were male and were of elder age-groups (mean age: 65.5 years, range: 32-76 years). Seven patients at first visited the department of respiratory medicine, and the remaining three patients were admitted without consulting the department of respiratory medicine before admission. Only patient had a history of pulmonary tuberculosis. Two patients were suspected of pulmonary tuberculosis on admission. Tubercle bacilli were positive sputum smear in 6 patients, sputum culture in 1, smear of bronchial washing in 4, and smear of BALF in 1. It took 12.7 days on the average from the admission to make a final diagnosis as pulmonary tuberculosis patients into a general hospital lacking TB ward were as follows: (1) As pulmonary TB was not suspected, Chest X-ray and sputum examination were not performed. (2) The admission was done due to another disease and respiratory symptoms were scarce. (3) Tuberculosis lesions on chest X-ray were harbored by pleural effusions and diffuse shadows. (4) Though pulmonary tuberculosis was suspected, a patient was admitted because of general prostration as sputum smear was negative. After admission, however, repeated sputum culture revealed positive results. (5) Pulmonary tuberculosis developed after the admission.

We report a case of minocycline-induced pneumonitis. A 30-year-old woman was treated with minocycline for mycoplasma pneumonia of the right upper lobe. About 15 days after starting treatment, she developed a productive cough, stridor, and dyspnea. The chest X-ray film showed pulmonary infiltration in the left middle lung field. Based on the clinical history and the detection of eosinophilia in the bronchoalveolar fluid, drug-induced pneumonitis was suspected. Treatment with minocycline was discontinued and prednisolone (20 mg/day) was started, after which her symptoms subsided and there was marked regression of the pulmonary infiltrates on chest X-ray films. The lymphocyte stimulation test for minocycline was negative, but the diagnosis was confirmed by a positive oral provocation test.

Williams-Campbell syndrome is a unique type of bronchiectasis which shows ballooning during expiration and collapse during inspiration. Its etiology is thought to be a congenital decrease in bronchial cartilage. We experienced two adult cases of Williams-Campbell syndrome. Since the mucociliary transport system was normal in both cases and neither case had chronic sinusitis, these cases differed from sino-bronchial syndrome. Cases of Williams-Campbell syndrome reported in Japan show characteristic bronchography, but a decrease in bronchial cartilage may or may not be present and its congenital nature is very difficult to demonstrate. We therefore advocate referring to such cases of bronchiectasis with these bronchographic characteristics Williams-Campbell-type bronchiectasis, even if a decrease in bronchial cartilage is not observed.