Publications by authors named "Takashi Makino"

95 Publications

Exploring the Loci Responsible for Awn Development in Rice through Comparative Analysis of All AA Genome Species.

Plants (Basel) 2021 Apr 8;10(4). Epub 2021 Apr 8.

Bioscience and Biotechnology Center, Nagoya University, Furo-cho, Chikusa, Nagoya, Aichi 464-8601, Japan.

Wild rice species have long awns at their seed tips, but this trait has been lost through rice domestication. Awn loss mitigates harvest and seed storage; further, awnlessness increases the grain number and, subsequently, improves grain yield in Asian cultivated rice, highlighting the contribution of the loss of awn to modern rice agriculture. Therefore, identifying the genes regulating awn development would facilitate the elucidation of a part of the domestication process in rice and increase our understanding of the complex mechanism in awn morphogenesis. To identify the novel loci regulating awn development and understand the conservation of genes in other wild rice relatives belonging to the AA genome group, we analyzed the chromosome segment substitution lines (CSSL). In this study, we compared a number of CSSL sets derived by crossing wild rice species in the AA genome group with the cultivated species ssp. . Two loci on chromosomes 7 and 11 were newly discovered to be responsible for awn development. We also found wild relatives that were used as donor parents of the CSSLs carrying the functional alleles responsible for awn elongation, () and . To understand the conserveness of and in wild rice relatives, we analyzed and sequences of 175 accessions among diverse AA genome species retrieved from the sequence read archive (SRA) database. Comparative sequence analysis demonstrated that most wild rice AA genome species maintained functional and , whereas most Asian rice cultivars have lost either or both functions. In addition, some different loss-of-function alleles of and were found in Asian cultivated species. These findings suggest that different combinations of dysfunctional alleles of and were selected after the speciation of . , and that two-step loss of function in and contributed to awnlessness in Asian cultivated rice.
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http://dx.doi.org/10.3390/plants10040725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068336PMC
April 2021

Optimal pollen stickiness to pollinators for maximizing paternal fitness: Increased number of recipient flowers or increased pollen deposition on recipient flowers?

J Theor Biol 2021 Apr 26;524:110731. Epub 2021 Apr 26.

Graduate School of Life Sciences, Tohoku University, Aoba, Sendai 980-8578, Japan. Electronic address:

A plant can sire more seeds by increasing the number of pollen recipient flowers or the amount of pollen deposited on recipient flowers. We theoretically analyzed how pollen stickiness contributes to paternal fitness through changing the pattern of pollen dispersal including both the number of recipient flowers and overall pollen deposition (the overall amount of pollen deposited on recipient flowers) in animal-pollinated plants. We developed a numerical model in which pollen stickiness to pollinators increases with production of expensive materials on pollen surfaces, and a high level of stickiness diminishes the proportions of pollen lost from a pollinator body during a flight and pollen deposited on a stigma during a visit. We found that the number of recipient flowers monotonically increased with increasing pollen stickiness allocation while overall pollen deposition was maximized at a certain amount of stickiness allocation. We demonstrated that evolutionarily stable pollen stickiness attained many recipient flowers at the expense of overall pollen deposition in most cases while it merely favored maximization of overall pollen deposition in all other cases. Sticky pollen evolved if pollinators were highly likely to drop pollen during flights and did not diffuse well. In this situation, the evolutionarily stable pattern of pollen dispersal was acquisition of many pollen recipient flowers rather than maximization of overall pollen deposition. Sticky pollen also evolved if additional sticking elements were moderately effective in increasing the force of adhesion to pollinators. Pollen stickiness has a significant effect on the pattern of pollen dispersal via the extent of pollen carryover, and our results suggest that plants maximize paternal fitness by giving pollen the optimal stickiness, which varies with pollinating partners.
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http://dx.doi.org/10.1016/j.jtbi.2021.110731DOI Listing
April 2021

Mediastinal tumor resection in a patient with spinocerebellar degeneration.

J Cardiothorac Surg 2020 Jul 29;15(1):197. Epub 2020 Jul 29.

Division of Chest Surgery, Department of Surgery, Toho University School of Medicine, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan.

Background: In spinocerebellar degeneration (SCD) patients, general and regional anesthesia may cause postoperative dysfunction of respiratory, nerve and muscle systems. We present the surgical case of thymoma developed in patient with SCD.

Case Presentation: A 47-year-old woman with spinocerebellar degeneration was admitted because of a well-defined mass measuring 48 × 31 mm in anterior mediastinum. She showed limb, truncal, ocular, and speech ataxia; hypotonia; areflexia; sensory disturbances; and muscle weakness. Her eastern cooperative oncology group performance status was 4. Surgical resection was performed via video-assisted thoracic surgery and under general anesthesia only without epidural analgesia. The mass was diagnosed as type B1 thymoma without capsular invasion (Masaoka stage I). The patients got a good postoperative course by cooperation with anesthesiologists and neurologists in perioperative managements. She has been well over 3 years of follow-up.

Conclusions: In conclusion, careful surgical and anesthesia management is essential for providing an uneventful postoperative course in patients with SCD. Especially, selection of minimal invasive approach and avoid diaphragmatic nerve damage are the most important points in surgical procedures.
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http://dx.doi.org/10.1186/s13019-020-01218-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7389681PMC
July 2020

Genetic factors for short life span associated with evolution of the loss of flight ability.

Ecol Evol 2020 Jun 29;10(12):6020-6029. Epub 2020 May 29.

Graduate School of Life Sciences Tohoku University Sendai Japan.

Acquisition or loss of flying ability is evolutionarily linked with maximum life span (MLS) in mammals and birds. Although ecological factors, such as extrinsic mortality, may lead to either shortened or extended life spans through natural selection, MLS is influenced by complex molecular and metabolic processes, and the genetic changes associated with flying ability that have led to either a longer or shorter MLS are unknown. Here, we examine the parallel evolution of flight in mammals and birds and investigate positively selected genes at branches where either the acquisition (in little brown bats and large flying foxes) or loss (in Adélie penguins, emperor penguins, common ostriches, emus, great spotted kiwis, little spotted kiwis, okarito brown kiwis, greater rheas, lesser rheas, and cassowaries) of flight abilities occurred. Although we found no shared genes under selection among all the branches of interest, 7 genes were found to be positively selected in 2 of the branches. Among the 7 genes, only is known to affect both life span and energy expenditure. The positively selected mutations detected in likely affected the functionality of the encoded protein. , which has been reported to simultaneously prolong life span and increase energy expenditure, could be responsible for the evolution of shortened MLS associated with the loss of flying ability.
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http://dx.doi.org/10.1002/ece3.6342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319159PMC
June 2020

Good syndrome with cytomegalovirus hepatitis: successful resection of Thymoma: a case report.

J Cardiothorac Surg 2020 Jun 15;15(1):141. Epub 2020 Jun 15.

Division of Chest Surgery, Toho University School of Medicine, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan.

Background: Good syndrome is a rare condition, manifesting as immunodeficiency due to hypogammaglobulinemia associated with thymoma. Herein, we present a patient with Good syndrome whose thymoma was resected after treatment of cytomegalovirus hepatitis.

Case Presentation: The patient was a 45-year-old woman presenting with fever, cough, and nasal discharge, and was diagnosed with thymoma and hypogammaglobulinemia. She subsequently developed cytomegalovirus hepatitis that was treated by immunoglobulin. After resolution of the hepatitis, she underwent thymectomy through a left anterior thoracotomy. Her postoperative course was uneventful, and while receiving ongoing immunoglobulin therapy, she has been doing well without signs of infection.

Conclusions: Management of infections is important for patients with Good syndrome. To minimize the risk of perioperative infection, we should take care while planning the surgical approach and procedure.
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http://dx.doi.org/10.1186/s13019-020-01187-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296951PMC
June 2020

Accumulation of Deleterious Mutations in Landlocked Threespine Stickleback Populations.

Genome Biol Evol 2020 04;12(4):479-492

Ecological Genetics Laboratory, National Institute of Genetics, Mishima, Shizuoka, Japan.

Colonization of new habitats often reduces population sizes and may result in the accumulation of deleterious mutations by genetic drift. Compared with the genomic basis for adaptation to new environments, genome-wide analysis of deleterious mutations in isolated populations remains limited. In the present study, we investigated the accumulation of deleterious mutations in five endangered freshwater populations of threespine stickleback (Gasterosteus aculeatus) in the central part of the mainland of Japan. Using whole-genome resequencing data, we first conducted phylogenomic analysis and confirmed at least two independent freshwater colonization events in the central mainland from ancestral marine ecotypes. Next, analyses of single nucleotide polymorphisms showed a substantial reduction of heterozygosity in freshwater populations compared with marine populations. Reduction in heterozygosity was more apparent at the center of each chromosome than the peripheries and on X chromosomes compared with autosomes. Third, bioinformatic analysis of deleterious mutations showed increased accumulation of putatively deleterious mutations in the landlocked freshwater populations compared with marine populations. For the majority of populations examined, the frequencies of putatively deleterious mutations were higher on X chromosomes than on autosomes. The interpopulation comparison indicated that the majority of putatively deleterious mutations may have accumulated independently. Thus, whole-genome resequencing of endangered populations can help to estimate the accumulation of deleterious mutations and inform us of which populations are the most severely endangered. Furthermore, analysis of variation among chromosomes can give insights into whether any particular chromosomes are likely to accumulate deleterious mutations.
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http://dx.doi.org/10.1093/gbe/evaa065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197494PMC
April 2020

Sensitivity to gene dosage and gene expression affects genes with copy number variants observed among neuropsychiatric diseases.

BMC Med Genomics 2020 03 29;13(1):55. Epub 2020 Mar 29.

Genome Medical Science Project (Toyama), National Center for for Global Health and Medicine, Tokyo, Japan.

Background: Copy number variants (CNVs) have been reported to be associated with diseases, traits, and evolution. However, it is hard to determine which gene should have priority as a target for further functional experiments if a CNV is rare or a singleton. In this study, we attempted to overcome this issue by using two approaches: by assessing the influences of gene dosage sensitivity and gene expression sensitivity. Dosage sensitive genes derived from two-round whole-genome duplication in previous studies. In addition, we proposed a cross-sectional omics approach that utilizes open data from GTEx to assess the effect of whole-genome CNVs on gene expression.

Methods: Affymetrix Genome-Wide SNP Array 6.0 was used to detect CNVs by PennCNV and CNV Workshop. After quality controls for population stratification, family relationship and CNV detection, 287 patients with narcolepsy, 133 patients with essential hypersomnia, 380 patients with panic disorders, 164 patients with autism, 784 patients with Alzheimer disease and 1280 healthy individuals remained for the enrichment analysis.

Results: Overall, significant enrichment of dosage sensitive genes was found across patients with narcolepsy, panic disorders and autism. Particularly, significant enrichment of dosage-sensitive genes in duplications was observed across all diseases except for Alzheimer disease. For deletions, less or no enrichment of dosage-sensitive genes with deletions was seen in the patients when compared to the healthy individuals. Interestingly, significant enrichments of genes with expression sensitivity in brain were observed in patients with panic disorder and autism. While duplications presented a higher burden, deletions did not cause significant differences when compared to the healthy individuals. When we assess the effect of sensitivity to genome dosage and gene expression at the same time, the highest ratio of enrichment was observed in the group including dosage-sensitive genes and genes with expression sensitivity only in brain. In addition, shared CNV regions among the five neuropsychiatric diseases were also investigated.

Conclusions: This study contributed the evidence that dosage-sensitive genes are associated with CNVs among neuropsychiatric diseases. In addition, we utilized open data from GTEx to assess the effect of whole-genome CNVs on gene expression. We also investigated shared CNV region among neuropsychiatric diseases.
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http://dx.doi.org/10.1186/s12920-020-0699-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104509PMC
March 2020

Toward improving prognosis prediction in patients undergoing small lung adenocarcinoma resection: Radiological and pathological assessment of diversity and intratumor heterogeneity.

Lung Cancer 2019 09 25;135:40-46. Epub 2019 Jun 25.

Division of Chest Surgery, Toho University School of Medicine, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan. Electronic address:

Objectives: Prediction of prognosis based on the ground-glass opacity (GGO) ratio for small (≤2 cm) lung adenocarcinomas is not completely accurate. The aim of this study was to clarify the diversity of small adenocarcinomas and to identify ways to more accurately predict prognosis.

Materials And Methods: We retrospectively reviewed 62 patients (64 lesions) that underwent lobectomy for small (≤2 cm) lung adenocarcinoma. Proportions of histological components were measured and the presence of tumor spread through air spaces (STAS) was assessed. The correlations between GGO and histological components were examined. Furthermore, histological components of pure GGO lesions were analyzed using CT values. The intratumor heterogeneity of programmed death ligand 1 (PD-L1) expression was analyzed in 40 lesions. Furthermore, the relationship between CT/histological findings and prognoses was analyzed.

Results: In 13 pure GGO lesions, 7 (53.8%) lesions contained invasive components such as papillary, acinar, solid, and colloid. Tumor spread through air spaces (STAS) was also found in pure GGO lesions. Pure GGO lesions containing invasive components (p =  0.002) and STAS-positive lesions (p =  0.011) demonstrated strongly higher CT value. Differences in expression of PD-L1 among histological subtypes were observed in four of six (66.7%) PD-L1 positive lesions. Patients with papillary component, positivity for STAS, or CT value ≥ -140.6 Hounsfield units (HU) had significant poorer prognoses than patients without those in disease-free survival analyses (p =  0.007, p =  0.048, p = 0.012). Patients with the CT value < -383.4 HU and GGO ≥ 50% did not have recurrence.

Conclusions: Invasive component and STAS can be present even in small GGO lesions, and patients with papillary components or STAS showed significantly poorer prognoses. STAS-positive lesions were strongly associated with a high CT value, and combined use of GGO ratio and CT value may be able to predict recurrences of lung cancer more accurately.
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http://dx.doi.org/10.1016/j.lungcan.2019.06.023DOI Listing
September 2019

Endangered island endemic plants have vulnerable genomes.

Commun Biol 2019 27;2:244. Epub 2019 Jun 27.

1Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai 980-8578 Japan.

Loss of genetic diversity is known to decrease the fitness of species and is a critical factor that increases extinction risk. However, there is little evidence for higher vulnerability and extinction risk in endangered species based on genomic differences between endangered and non-endangered species. This is true even in the case of functional loci, which are more likely to relate to the fitness of species than neutral loci. Here, we compared the genome-wide genetic diversity, proportion of duplicated genes (), and accumulation of deleterious variations of endangered island endemic (EIE) plants from four genera with those of their non-endangered (NE) widespread congeners. We focused on exhaustive sequences of expressed genes obtained by RNA sequencing. Most EIE species exhibited significantly lower genetic diversity and than NE species. Additionally, all endangered species accumulated deleterious variations. Our findings provide new insights into the genomic traits of EIE species.
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http://dx.doi.org/10.1038/s42003-019-0490-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597543PMC
May 2020

Resection of a Superior Mediastinal Mature Teratoma Using Intraoperative Neural Monitoring.

Ann Thorac Surg 2019 11 11;108(5):e287-e288. Epub 2019 Apr 11.

Division of Chest Surgery, Department of Surgery, Toho University School of Medicine, Tokyo, Japan. Electronic address:

A 33-year-old woman presented with a right cervical mass. Contrast computed tomography showed a multilocular tumor with a clear border and heterogeneous contents including fat and calcification. The tumor was located adjacent to the vagus and recurrent nerves. To avoid injury of these nerves, we resected the tumor through a median sternotomy and right cervical lateral incision. Intraoperative neural monitoring was performed using an NIM TriVantage EMG tube (Medtronic, Minneapolis, MN). After the surgery, no neuropathy such as hoarseness was recognized. Pathological diagnosis showed a benign mature teratoma. Intraoperative neural monitoring is useful for superior mediastinal surgery around the vagus and recurrent nerves.
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http://dx.doi.org/10.1016/j.athoracsur.2019.03.035DOI Listing
November 2019

Invasive invertebrates associated with highly duplicated gene content.

Mol Ecol 2019 04 27;28(7):1652-1663. Epub 2019 Feb 27.

Graduate School of Life Sciences, Tohoku University, Sendai, Japan.

Invasion of alien species has led to serious problems, including the destruction of native ecosystems. In general, invasive species adapt to new environments rapidly, suggesting that they have high genetic diversity that can directly influence environmental adaptability. However, it is not known how genomic architecture causes genetic diversity that leads to invasiveness. Recent studies have showed that the proportion of duplicated genes (P ) in whole animal genomes correlate with environmental variability within a habitat. Here, we show that P and propagule size significantly explain the differences in species categories (invasive species, noninvasive species, and parasites). P correlated negatively with the propagule size. The residual values of regression of P on propagule size revealed that the invasive species had higher P values and larger propagule size than those of the noninvasive species, whereas the parasites had lower P values and smaller propagule size than those of others. There were no correlations between the invasive species and other genomic factors including the genome size, number of genes, and certain gene families. Our results suggest that the P values of a genome might be a potential genomic source causing genetic variations for adaptation to diverse environments. The results also showed that the invasiveness status of a species would be predicted by the residual values of regression of P on propagule size. Our innovative approach provides a measure to estimate the environmental adaptability of organisms based on genomic data.
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http://dx.doi.org/10.1111/mec.15019DOI Listing
April 2019

JmjC Domain-Encoding Genes Are Conserved in Highly Regenerative Metazoans and Are Associated with Planarian Whole-Body Regeneration.

Genome Biol Evol 2019 02;11(2):552-564

Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai, Japan.

The capacity for regeneration varies greatly among metazoans, yet little is known about the evolutionary processes leading to such different regeneration abilities. In particular, highly regenerative species such as planarians and cnidarians can regenerate the whole body from an amputated fragment; however, a common molecular basis, if any, among these species remains unclear. Here, we show that genes encoding Jumonji C (JmjC) domain-containing proteins are associated with high regeneration ability. We classified 132 fully sequenced metazoans into two groups with high or low regeneration abilities and identified 118 genes conserved in the high regenerative group that were lost in species in the low regeneration group during evolution. Ninety-six percent of them were JmjC domain-encoding genes. We denoted the candidate genes as high regenerative species-specific JmjC domain-encoding genes (HRJDs). We observed losses of HRJDs in Helobdella robusta, which lost its high regeneration ability during evolution based on phylogenetic analysis. By RNA sequencing analyses, we observed that HRJD orthologs were differentially expressed during regeneration in two Cnidarians, as well as Platyhelminthes and Urochordata, which are highly regenerative species. Furthermore, >50% of the head and tail parts of amputated planarians (Dugesia japonica) died during regeneration after RNA interference of HRJD orthologs. These results indicate that HRJD are strongly associated with a high regeneration ability in metazoans. HRJD paralogs regulate gene expression by histone demethylation; thus, HRJD may be related to epigenetic regulation controlling stem cell renewal and stem cell differentiation during regeneration. We propose that HRJD play a central role in epigenetic regulation during regeneration.
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http://dx.doi.org/10.1093/gbe/evz021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390904PMC
February 2019

The role of video-assisted thoracoscopic surgery in the diagnosis of interstitial lung disease.

Sarcoidosis Vasc Diffuse Lung Dis 2019 1;36(2):148-156. Epub 2019 May 1.

Department of Respiratory Medicine.

Background: When a clinical context is indeterminate for idiopathic pulmonary fibrosis (IPF), or a chest high-resolution computed tomography (HRCT) pattern is not indicative of typical or probable usual interstitial pneumonia (UIP) in patients with interstitial lung disease (ILD), surgical lung biopsy should be considered to make a confident diagnosis on the basis of multidisciplinary diagnosis (MDD).

Aim: The aim of this study was to evaluate the role and safety of video-assisted thoracoscopic surgery (VATS) in patients with ILD.

Methods: A total of 143 patients with ILD underwent VATS at Toho University Medical Center Omori Hospital between March 2004 and April 2017. We conducted a retrospective study on the usefulness and safety of VATS in the diagnosis of ILD under MDD.

Results: The 30-day mortality was 0%. The postoperative complication rate was 12.6%, which included 5 cases of pneumothorax after discharge (3.5%), 4 cases of prolonged air leakage (2.8%), and 2 cases of acute exacerbation (1.4%). Three of 9 cases (33.3%) complicated by pneumothorax after discharge or prolonged air leakage were resected specimens of pleuroparenchymal fibroelastosis (PPFE). Two patients had acute exacerbation, who were ultimately diagnosed as having idiopathic unclassifiable IP and had histologically significant irregular dense fibrosis and numerous fibroblastic foci. The comparison between chest HRCT and histopathological findings revealed 55 cases of possible UIP [UIP (45%), NSIP (25%), and unclassifiable IP (29%)] and 21 cases of inconsistent with UIP [UIP (10%), NSIP (33%), organizing pneumonia (10%), unclassifiable IP (24%), and PPFE (24%)].

Conclusion: VATS can be safely performed to obtain a confident diagnosis for appropriate treatment strategies in patients with ILD.
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http://dx.doi.org/10.36141/svdld.v36i2.7797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247103PMC
July 2020

New risk scoring system for predicting acute exacerbation of interstitial pneumonia after chemotherapy for lung cancer associated with interstitial pneumonia.

Lung Cancer 2018 11 7;125:253-257. Epub 2018 Oct 7.

Division of Respiratory Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan.

Background: Fatal acute exacerbation (AE) of interstitial pneumonia (IP) sometimes occurs after chemotherapy for lung cancer. We developed and evaluated a scoring system for assessing AE risk after chemotherapy in patients with lung cancer associated with IP.

Methods: A review of medical records identified 109 patients with primary lung cancer associated with IP who had received chemotherapy at our center during the period from June 2007 through September 2017. We developed a model to score AE risk after chemotherapy in this patient group, and logistic regression was used to evaluate the model.

Results: The anticancer agent score was determined by using AE rates reported in past studies. The risk score was calculated with the following formula: (1 × anticancer agent score) + (3 × smoking history [>70 pack-years]) + (4 × history of steroid use) + (3 × %diffusing capacity of lung carbon monoxide [<50%]). Patients were then classified into three groups. The AE incidence rate was 12% for a risk score of 0-5, 47% for a score of 6-10, and 66.7% for a score of ≥11. The sensitivity of the scoring system was 78.6% and specificity was 67.8%.

Conclusions: The present scoring system was able to identify IP patients at high risk for AE after chemotherapy for lung cancer associated with IP.
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http://dx.doi.org/10.1016/j.lungcan.2018.10.008DOI Listing
November 2018

Factors affecting interspecific differences in genetic divergence among populations of lizards in Cuba.

Zoological Lett 2018 9;4:21. Epub 2018 Aug 9.

1Graduate School of Life Sciences, Tohoku University, Sendai, Japan.

Background: Geographical patterns and degrees of genetic divergence among populations differ between species, reflecting relative potentials for speciation or cladogenesis and differing capacities for environmental adaptation. Identification of factors that contribute to genetic divergence among populations is important to the understanding of why some species exhibit greater interpopulation genetic divergence. In this study, we calculated the mean pairwise genetic distances among populations as species' average genetic divergence by a phylogeny using nuclear and mitochondrial genes of 303 individuals from 33 Cuban species and estimated species ages by another phylogeny using nuclear and mitochondrial genes of 51 Cuban and 47 non-Cuban species. We identified factors that influence species' differences in genetic divergence among 26 species of lizards from Cuba. Species ages, environmental heterogeneity within species ranges, and ecomorph types were considered as factors affecting average genetic divergences among populations.

Results: The phylogenies presented in this study provide the most comprehensive sampling of Cuban species to date. The phylogeny showed more conservative evolution of ecomorphs within Cuba and identified twig anoles as a monophyletic group. Subsequent Phylogenetic Generalized Least Squares (PGLS) analyses showed that species age was positively correlated with species' average genetic divergence among populations.

Conclusion: Although previous studies have focused on factors affecting genetic divergence within species, the present study showed for the first time that species differences in genetic divergence could be largely affected by species age.
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http://dx.doi.org/10.1186/s40851-018-0107-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085692PMC
August 2018

Lobectomy for lung cancer in a myelodysplastic syndrome patient with decreasing platelet aggregation: report of a case.

J Cardiothorac Surg 2018 Jul 24;13(1):89. Epub 2018 Jul 24.

Division of Chest Surgery, Toho University School of Medicine, Tokyo, Japan.

Background: Myelodysplastic syndromes (MDS) are clonal stem cell disorders of the bone marrow. Most patients with MDS have a high risk of bleeding. Thrombocytopenia and defective platelet aggregation contribute to bleeding. We report a surgical case of a patient with lung cancer concomitant with MDS.

Case Presentation: A 72-year-old man presented to our hospital because of an abnormal shadow on chest x-ray suggesting a primary lung cancer. A peripheral blood smear examination found giant platelets without thrombocytopenia. He was diagnosed with MDS by bone marrow biopsy, and showed defective platelet aggregation despite a normal bleeding time. The patient underwent left lower lobectomy and transfusion of platelets because of chest wall bleeding.

Conclusions: We demonstrated that ordering platelet preparations might be desirable for an MDS patient with defective platelet aggregation who will undergo surgery, even for a normal platelet count and bleeding time.
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http://dx.doi.org/10.1186/s13019-018-0777-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057011PMC
July 2018

Evolution of Gustatory Receptor Gene Family Provides Insights into Adaptation to Diverse Host Plants in Nymphalid Butterflies.

Genome Biol Evol 2018 06;10(6):1351-1362

Graduate School of Life Sciences, Tohoku University, Sendai, Japan.

The host plant range of herbivorous insects is a major aspect of insect-plant interaction, but the genetic basis of host range expansion in insects is poorly understood. In butterflies, gustatory receptor genes (GRs) play important roles in host plant selection by ovipositing females. Since several studies have shown associations between the repertoire sizes of chemosensory gene families and the diversity of resource use, we hypothesized that the increase in the number of genes in the GR family is associated with host range expansion in butterflies. Here, we analyzed the evolutionary dynamics of GRs among related species, including the host generalist Vanessa cardui and three specialists. Although the increase of the GR repertoire itself was not observed, we found that the gene birth rate of GRs was the highest in the lineage leading to V. cardui compared with other specialist lineages. We also identified two taxon-specific subfamilies of GRs, characterized by frequent lineage-specific duplications and higher non-synonymous substitution rates. Together, our results suggest that frequent gene duplications in GRs, which might be involved in the detection of plant secondary metabolites, were associated with host range expansion in the V. cardui lineage. These evolutionary patterns imply that the capability to perceive various compounds during host selection was favored during adaptation to diverse host plants.
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http://dx.doi.org/10.1093/gbe/evy093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007367PMC
June 2018

PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma.

Oncol Rep 2018 Jul 16;40(1):331-338. Epub 2018 May 16.

Division of Respiratory Medicine, Toho University School of Medicine, Tokyo 143-8541, Japan.

Molecular mechanisms of programmed death-ligand 1 (PD-L1) mRNA expression and roles of apoptosis and biomarkers are poorly understood in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients. Thirty-three patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (exon 19 deletion in 16, L858R in 15, G719C in 2 patients) treated with gefitinib were studied. PD-L1 mRNA expression of formalin-fixed paraffin-embedded paratumoral and intratumoral tissues was quantified by PCR. Correlations of PD-L1 mRNA expression with BIM, p53 upregulated modular of apoptosis (PUMA), human epidermal growth factor receptor 2 (HER2), mesenchymal-epithelial transition (MET), EGFR, and vascular endothelial growth factor A (VEGFA) were determined. Eleven of the 33 patients (33.3%) and 14/33 patients (42.4%) expressed intratumoral and paratumoral PD-L1 mRNA, respectively. Patients with intratumoral PD-L1 mRNA expression had significantly higher BIM and lower VEGFA expression compared with paratumoral PD-L1 mRNA patients (P=0.049, P=0.009). PD-L1 mRNA expression was not associated with the expression of PUMA, HER2, EGFR and MET but was positively correlated with BIM expression (r=0.41, P=0.017) and inversely correlated with VEGFA expression (r=-0.33, P=0.043). Patients with intratumoral PD-L1 mRNA expression had significantly shorter median progression-free survival (PFS) after gefitinib therapy compared with no PD-L1 expression (255 vs. 732 days, respectively; P=0.032). Thus, PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma was associated with BIM and VEGFA mRNA expression and with shorter PFS after gefitinib therapy.
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http://dx.doi.org/10.3892/or.2018.6442DOI Listing
July 2018

Long-acting muscarinic antagonist and long-acting β2-agonist therapy to optimize chronic obstructive pulmonary disease prior to lung cancer surgery.

Mol Clin Oncol 2018 May 26;8(5):647-652. Epub 2018 Mar 26.

Division of Chest Surgery, Toho University School of Medicine, Ota, Tokyo 143-8541, Japan.

Bronchodilators are essential for the perioperative management of patients with chronic obstructive pulmonary disease (COPD) undergoing surgery for lung cancer. The objective of the present study was to examine whether the usage of a long-acting β2-agonist (LABA) with a long-acting muscarinic antagonist (LAMA) could optimize preoperative lung function and reduce the risk for postoperative pulmonary complications. Thirty-two consecutive patients with moderate-to-severe COPD who underwent a lobectomy for lung cancer and received preoperative LAMA (n=19) or LAMA/LABA (n=13) therapy between January 2005 and December 2015 were enrolled in this retrospective study. The improvement of preoperative pulmonary function and the postoperative morbidity were compared between the patients with preoperative LAMA, and LAMA/LABA therapy. Increases in the forced expiratory volume in one second (FEV) were significantly larger in the LAMA/LABA group than in the LAMA group (0.26±0.05 l vs. 0.07±0.05 l; P=0.0145). More patients in the LAMA/LABA group than in the LAMA group showed a marked improvement of >10% in %FEV after bronchodilators (85 vs. 32%; P=0.0046). The incidence of postoperative pneumonia was significantly lower in the LAMA/LABA group than in the LAMA group (0 vs. 26%; P=0.044). In conclusion, the present study showed that preoperative LAMA/LABA therapy was associated with larger improvements in preoperative pulmonary function and less postoperative pneumonia than LAMA therapy. These results may lead to greater improvements in FEV and less postoperative pneumonia by encouraging preoperative LAMA/LABA therapy in this patient population.
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http://dx.doi.org/10.3892/mco.2018.1595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920355PMC
May 2018

Giant thymoma successfully resected via median sternotomy and anterolateral thoracotomy: a case report.

J Cardiothorac Surg 2018 Apr 10;13(1):26. Epub 2018 Apr 10.

Division of Chest Surgery, Toho University School of Medicine, Tokyo, Japan.

Background: Some patients with thymoma present with a very large mass in the thoracic cavity. Although the most effective treatment for thymoma is surgical resection, it is difficult to perform because of the size of the tumor and the infiltration of tumor into the surrounding organs and vessels. We report a patient with a giant thymoma that was completely resected via a median sternotomy and left anterolateral thoracotomy.

Case Presentation: A 63-year-old woman presented with a mass in the left thoracic cavity that was incidentally found on a chest X-ray. Chest computed tomography revealed a giant mass (16 × 10 cm) touching the chest wall and diaphragm and pressed against the heart and left upper pulmonary lobe. Complete resection was performed via a median sternotomy and left anterolateral thoracotomy. The tumor was histologically diagnosed as a WHO type B2 thymoma, Masaoka stage II.

Conclusions: Giant thymomas tend to grow expansively without invasion into surrounding organs and vessels. Surgical resection that employs an adequate approach must be considered, regardless of the size of the tumor.
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http://dx.doi.org/10.1186/s13019-018-0711-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5894157PMC
April 2018

Comparisons of behavioural and TRPA1 heat sensitivities in three sympatric Cuban Anolis lizards.

Mol Ecol 2018 05 23;27(9):2234-2242. Epub 2018 Apr 23.

Department of Ecology and Evolutionary Biology, Graduate School of Life Sciences, Tohoku University, Sendai, Japan.

Thermal tolerances of organisms play a role in defining geographic ranges and occurrence of species. In Cuba, three sympatric species of Anolis lizards (Anolis allogus, Anolis homolechis and Anolis sagrei) inhabit different thermal microhabitats. A previous study found that these species showed distinct gene expression patterns in response to temperature stimuli, suggesting the genetically distinct thermal physiology among species. To investigate whether the Anolis species inhabiting locally distinct thermal habitats diverge their thermal tolerances, we first conducted behavioural experiments to analyse the temperatures at which the three Anolis species escape from heat source. Then, for each of the three species, we isolated cDNA encoding a putative molecular heat sensor, transient receptor potential ion channel ankyrin 1 (TRPA1), which has been suggested to play a role on eliciting behavioural responses to heat stimuli. We performed electrophysiological analysis to quantify activation temperature of Anolis TRPA1 to see whether the pattern of divergence in TRPA1 responses is congruent with that of divergence in behavioural responses. We found that temperatures triggering behavioural and TRPA1 responses were significantly lower for shade-dwelling species (A. allogus) than for sun-dwelling species (A. homolechis and A. sagrei). The ambient temperature of shade habitats where A. allogus occurs stays relatively cool compared to that of open habitats where A. homolechis and A. sagrei occur and bask. The high temperature thresholds of A. homolechis and A. sagrei may reflect their heat tolerances that would benefit these species to inhabit the open habitats.
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http://dx.doi.org/10.1111/mec.14572DOI Listing
May 2018

Elevated Proportions of Deleterious Genetic Variation in Domestic Animals and Plants.

Genome Biol Evol 2018 01;10(1):276-290

Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Sweden.

A fraction of genetic variants segregating in any population are deleterious, which negatively impacts individual fitness. The domestication of animals and plants is associated with population bottlenecks and artificial selection, which are predicted to increase the proportion of deleterious variants. However, the extent to which this is a general feature of domestic species is unclear. Here, we examine the effects of domestication on the prevalence of deleterious variation using pooled whole-genome resequencing data from five domestic animal species (dog, pig, rabbit, chicken, and silkworm) and two domestic plant species (rice and soybean) compared with their wild ancestors. We find significantly reduced genetic variation and increased proportion of nonsynonymous amino acid changes in all but one of the domestic species. These differences are observable across a range of allele frequencies, both common and rare. We find proportionally more single nucleotide polymorphisms in highly conserved elements in domestic species and a tendency for domestic species to harbor a higher proportion of changes classified as damaging. Our findings most likely reflect an increased incidence of deleterious variants in domestic species, which is most likely attributable to population bottlenecks that lead to a reduction in the efficacy of selection. An exception to this pattern is displayed by European domestic pigs, which do not show traces of a strong population bottleneck and probably continued to exchange genes with wild boar populations after domestication. The results presented here indicate that an elevated proportion of deleterious variants is a common, but not ubiquitous, feature of domestic species.
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http://dx.doi.org/10.1093/gbe/evy004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786255PMC
January 2018

Inferring evolutionary responses of Anolis carolinensis introduced into the Ogasawara archipelago using whole genome sequence data.

Sci Rep 2017 12 21;7(1):18008. Epub 2017 Dec 21.

Department of Ecology and Evolutionary Biology, Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai, 980-8578, Japan.

Invaded species often can rapidly expand and establish in novel environments through adaptive evolution, resulting in devastating effects on native communities. However, it is unclear if genetic variation at whole-genomic levels is actually reduced in the introduced populations and which genetic changes have occurred responding to adaptation to new environments. In the 1960s, Anolis carolinensis was introduced onto one of the Ogasawara Islands, Japan, and subsequently expanded its range rapidly throughout two of the islands. Morphological comparison showed that lower hindlimb length in the introduced populations tended to be longer than those in its native Florida populations. Using re-sequenced whole genomic data, we estimated that the effective population size at the time of introduction was actually small (less than 50). We also inferred putative genomic regions subject to natural selection after this introduction event using SweeD and a method based on Tajima's D, π and F . Five candidate genes that were potentially subject to selection were estimated by both methods. The results suggest that there were standing variations that could potentially contribute to adaptation to nonnative environments despite the founder population being small.
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http://dx.doi.org/10.1038/s41598-017-17852-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5740155PMC
December 2017

HSF1 and HSF3 cooperatively regulate the heat shock response in lizards.

PLoS One 2017 7;12(7):e0180776. Epub 2017 Jul 7.

Departments of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Minami-Kogushi, Ube, Japan.

Cells cope with temperature elevations, which cause protein misfolding, by expressing heat shock proteins (HSPs). This adaptive response is called the heat shock response (HSR), and it is regulated mainly by heat shock transcription factor (HSF). Among the four HSF family members in vertebrates, HSF1 is a master regulator of HSP expression during proteotoxic stress including heat shock in mammals, whereas HSF3 is required for the HSR in birds. To examine whether only one of the HSF family members possesses the potential to induce the HSR in vertebrate animals, we isolated cDNA clones encoding lizard and frog HSF genes. The reconstructed phylogenetic tree of vertebrate HSFs demonstrated that HSF3 in one species is unrelated with that in other species. We found that the DNA-binding activity of both HSF1 and HSF3 in lizard and frog cells was induced in response to heat shock. Unexpectedly, overexpression of lizard and frog HSF3 as well as HSF1 induced HSP70 expression in mouse cells during heat shock, indicating that the two factors have the potential to induce the HSR. Furthermore, knockdown of either HSF3 or HSF1 markedly reduced HSP70 induction in lizard cells and resistance to heat shock. These results demonstrated that HSF1 and HSF3 cooperatively regulate the HSR at least in lizards, and suggest complex mechanisms of the HSR in lizards as well as frogs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180776PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501597PMC
October 2017

Diffuse fluorodeoxyglucose-positron uptake in the bone marrow of a patient with granulocyte colony-stimulating factor-producing pleomorphic carcinoma of the lung: A case report.

Mol Clin Oncol 2017 Jul 29;7(1):103-106. Epub 2017 May 29.

Division of Chest Surgery, Toho University School of Medicine, Tokyo 143-8541, Japan.

The current study presents the case of a 66-year-old male presenting with fever and chest pain. Chest enhanced computed tomography scanning revealed a mass shadow in the right upper lobe with chest wall invasion. 18-Fluorodeoxyglucose-positron emission tomography (FDG-PET) identified the localized uptake of the mass lesion in the right upper lobe, in addition to diffuse uptake by the bone marrow. The laboratory data on admission revealed marked leukocytosis and an elevated C-reactive protein level (CRP). Serum concentrations of granulocyte colony-stimulating factor (G-CSF) and interleukin 6 were increased. Based on a clinical diagnosis of non-small cell lung cancer (c-T3N0M0 stage IIB), the patient underwent right upper lobectomy with chest wall resection. The histological examination showed a pulmonary pleomorphic carcinoma. Immunohistochemical analysis of the resected tumor tissues revealed positive staining for G-CSF. The patient's high-grade fever, leukocytosis, and elevated CRP level rapidly subsided following the resection. This confirmed that the tumor was a G-CSF-producing pulmonary pleomorphic carcinoma. Five months after the resection, the diffuse FDG uptake in the bone marrow was absent, even with the presence of a small pulmonary metastasis and marginal serum G-CSF elevation. Diffuse FDG uptake in bone marrow induced by G-CSF producing pleomorphic carcinoma must be taken into consideration, in order for it not to be misinterpreted as diffuse bone marrow metastases or hematologic malignancy.
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http://dx.doi.org/10.3892/mco.2017.1271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492683PMC
July 2017

Inference of Causative Genes for Alzheimer's Disease Due to Dosage Imbalance.

Mol Biol Evol 2017 09;34(9):2396-2407

Department of Ecology and Evolutionary Biology, Graduate School of Life Sciences, Tohoku University, Sendai, Japan.

Copy number variations (CNVs) have recently drawn attention as an important genetic factor for diseases, especially common neuropsychiatric disorders including Alzheimer's disease (AD). Because most of the pathogenic CNV regions overlap with multiple genes, it has been challenging to identify the true disease-causing genes amongst them. Notably, a recent study reported that CNV regions containing ohnologs, which are dosage-sensitive genes, are likely to be deleterious. Utilizing the unique feature of ohnologs could be useful for identifying causative genes with pathogenic CNVs, however its effectiveness is still unclear. Although it has been reported that AD is strongly affected by CNVs, most of AD-causing genes with pathogenic CNVs have not been identified yet. Here, we show that dosage-sensitive ohnologs within CNV regions reported in patients with AD are related to the nervous system and are highly expressed in the brain, similar to other known susceptible genes for AD. We found that CNV regions in patients with AD contained dosage-sensitive genes, which are ohnologs not overlapping with control CNV regions, frequently. Furthermore, these dosage-sensitive genes in pathogenic CNV regions had a strong enrichment in the nervous system for mouse knockout phenotype and high expression in the brain similar to the known susceptible genes for AD. Our results demonstrated that selecting dosage-sensitive ohnologs out of multiple genes with pathogenic CNVs is effective in identifying the causative genes for AD. This methodology can be applied to other diseases caused by dosage imbalance and might help to establish the medical diagnosis by analysis of CNVs.
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http://dx.doi.org/10.1093/molbev/msx183DOI Listing
September 2017

Factors restricting the range expansion of the invasive green anole on Okinawa Island, Japan.

Ecol Evol 2017 06 10;7(12):4357-4366. Epub 2017 May 10.

Department of Ecology and Evolutionary Biology Graduate School of Life Sciences Tohoku University Sendai Miyagi Japan.

The green anole invaded the Ogasawara Islands in Japan, drove various native species to extinction, and its distribution expanded 14 years after initial establishment. invaded Okinawa Island, but it has not expanded its distribution in more than 25 years, although its density is extremely high in the southern region. To determine whether has the potential to expand its distribution on Okinawa Island, we performed phylogenetic analysis of mitochondrial ND2 DNA sequences to study the origin of that invaded Okinawa Island. We further used a species distribution model (MaxEnt) based on the distribution of native populations in North America to identify ecologically suitable areas on Okinawa Island. Nucleotide sequence analysis shows that the invader originated in the western part of the Gulf Coast and inland areas of the United States and that a portion of the anoles on Okinawa was not introduced via the Ogasawara Islands. The MaxEnt predictions indicate that most areas in Okinawa Island are suitable for . Therefore, may have the potential to expand its distribution in Okinawa Island. The predictions indicate that habitat suitability is high in areas of high annual mean temperature and urbanized areas. The values of precipitation in summer in the northern region of Okinawa Island were higher compared with those of North America, which reduced the habitat suitability in Okinawa Island. Adaptation to low temperatures, an increase in the mean temperature through global warming, and an increase in open environments through land development will likely expand the distribution of in Okinawa Island. Therefore, we must continue to monitor the introduced populations and be alert to the possibility that city planning that increases open environments may cause their range to expand.
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http://dx.doi.org/10.1002/ece3.3002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478079PMC
June 2017

The Effects of CpG Densities around Transcription Start Sites on Sex-Biased Gene Expression in Poecilia reticulata.

Genome Biol Evol 2017 05;9(5):1204-1211

Department of Ecology and Evolutionary Biology, Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai, Japan.

As most genes are shared between females and males, DNA methylation is assumed to play a crucial role in sex-biased gene expression. DNA methylation exclusively occurs at CpG dinucleotides, and therefore, we would expect that CpG density around transcription start sites (TSSs) relate to sex-biased gene expression. Here we investigated the relationship between CpG densities around TSSs and the ratio of gene expression levels between sexes in the guppy (Poecilia reticulata), which displays remarkable sexual dimorphisms. We found that genes with sex-biased gene expression had different CpG densities downstream of TSSs compared with genes lacking sex-biased gene expression. Intriguingly, male-biased expression genes with intermediate CpG density downstream of TSSs exhibited greater differences in gene expression between sexes in the gonad and tail. Our findings suggested the possibility that CpGs around TSSs, especially in the downstream regions, play a crucial role in sex-biased gene expression through DNA methylation.
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http://dx.doi.org/10.1093/gbe/evx083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554587PMC
May 2017

Primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue with multiple pure ground-glass opacities: a case report.

J Cardiothorac Surg 2017 Jan 25;12(1). Epub 2017 Jan 25.

Division of Chest Surgery, Toho University School of Medicine, Tokyo, Japan.

Background: Primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade B cell lymphoma that is a type of non-Hodgkin lymphoma and a type of primary pulmonary malignant lymphoma. MALT lymphomas affecting the lung show various findings on chest computed tomography, which range from typical nodules or areas of consolidation to findings that are extremely rare in pulmonary MALT lymphomas, such as pure ground-glass opacities throughout the lung.

Case Presentation: A 35-year-old woman was found to have a few shadows with ground glass opacities on chest computed tomography (CT) in 2012. A shadow in right S10 that was initially very small increased in size over time, and was 14 × 8 mm in 2015. Other shadows also appeared. Because lung adenocarcinoma was suspected, the patient underwent video-assisted thoracoscopic surgery with a right wedge resection of the lower lobe that included the largest nodule in S10 and other nodules. Histopathological examination of the right S10 and other lesions revealed small- or medium-sized lymphocyte-like cells that were located in the alveolar interseptal spaces. The alveolar walls remained intact. Immunohistochemical staining showed that tumor cells were positive for CD20, CD79a, and BCL2 expression. The lesions were diagnosed as extranodal marginal zone B-cell lymphoma of MALT.

Conclusions: We think that the ground glass opacities on CT were accounted for by MALT lesions that contained intact alveolar air spaces. The patient has remained well during 12 months of follow up after surgery. Although she did not receive chemotherapy because the MALT lymphoma lesions have been stable without progression, the patient is kept under close observation because of potential progression of the disease.
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http://dx.doi.org/10.1186/s13019-017-0565-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264446PMC
January 2017