Biodiversity and Constrained Information Dynamics in Ecosystems: A Framework for Living Systems.

The increase in ecosystem biodiversity can be perceived as one of the universal processes converting energy into information across a wide range of living systems. This study delves into the dynamics of living systems, highlighting the distinction between ex post adaptation, typically associated with natural selection, and its proactive counterpart, ex ante adaptability. Through coalescence experiments using synthetic ecosystems, we (i) quantified ecosystem stability, (ii) identified correlations between some biodiversity indexes and the stability, (iii) proposed a mechanism for increasing biodiversity through moderate inter-ecosystem interactions, and (iv) inferred that the information carrier of ecosystems is species composition, or merged genomic information. Additionally, it was suggested that (v) changes in ecosystems are constrained to a low-dimensional state space, with three distinct alteration trajectories-fluctuations, rapid environmental responses, and long-term changes-converging into this state space in common. These findings suggest that daily fluctuations may predict broader ecosystem changes. Our experimental insights, coupled with an exploration of living systems' information dynamics from an ecosystem perspective, enhance our predictive capabilities for natural ecosystem behavior, providing a universal framework for understanding a broad spectrum of living systems.

[Refractory primary myeloid sarcoma of the breast with MLL-AF9 rearrangement].

A 28-year-old woman presented with a right breast mass and axillary lymphadenopathy. Biopsy of the breast mass revealed myeloid sarcoma (MS) staining positive for CD4, CD13, CD33, and CD68/KP-1. Bone marrow aspiration revealed leukemic cell infiltration (9%). Leukemic cells possessed cytogenetic abnormalities of +8 and t(9;11)(p22;q23) with +22 (lymph node only), and molecular analyses confirmed the MLL-AF9 fusion gene. After induction chemotherapy and 2(nd) consolidation therapy, complete remission was maintained. However, during consolidation radiotherapy for the breast mass, the disease progressed in both the breast and bone marrow. She received re-induction therapy and proceeded to allogeneic stem cell transplantation. However, the disease relapsed in the breast soon after transplantation, and she died from disease progression. Trisomy 8 and the MLL-AF9 fusion gene have been reported in cases with MS in the breast. Trisomy 22 found additionally and exclusively in the extramedullary lesion implies extramedullary progression of MS from the medullary site of origin and may have been associated with the distinctive therapy resistance of these lesions in our case.

A case of gray platelet syndrome masked by immune thrombocytopenia at presentation.

We report a case of gray platelet syndrome (GPS) associated with immune thrombocytopenia (ITP) at presentation. A 22-year-old male patient presenting with petechiae on his limbs was diagnosed with ITP due to a gradual decrease of his platelet count to a minimum of 26 × 10(9) /liter and an elevated platelet-associated IgG (PA-IgG) level in the absence of any other specific cause of thrombocytopenia. Administration of prednisolone increased his platelet count, but this dropped again to approximately 50 × 10(9) /liter as the dose was tapered, and remained at the same level after the treatment was terminated. Thirteen years later, we reassessed the cause of the thrombocytopenia because the PA-IgG level was found to be within the normal range. There were large hypogranular platelets on the blood film and a deficit of α-granules in the platelets on electron microscopy. On this basis, we diagnosed his thrombocytopenia as GPS. To our knowledge, this is the first report of a GPS case associated with ITP at presentation. This case illustrates the importance of carefully reviewing blood film results in the differential diagnosis of thrombocytopenia.

Synthetic model ecosystem of 12 cryopreservable microbial species allowing for a noninvasive approach.

Simultaneous understanding of both population and ecosystem dynamics is crucial in an era marked by the degradation of ecosystem services. Experimental ecosystems are a powerful tool for understanding these dynamics; however, they often face technical challenges, typically falling into two categories: "complex but with limited replicability microcosms" and "highly replicable but overly simplistic microcosms." Herein, we present a high-throughput synthetic microcosm system comprising 12 functionally and phylogenetically diverse microbial species. These species are axenically culturable, cryopreservable, and can be measured noninvasively via microscopy, aided by machine learning. This system includes prokaryotic and eukaryotic producers and decomposers, and eukaryotic consumers to ensure functional redundancy. Our model system exhibited key features of a complex ecosystem: (i) various positive and negative interspecific interactions, (ii) higher-order interactions beyond two-species dynamics, (iii) probabilistic dynamics leading to divergent outcomes, and (iv) stable nonlinear transitions. We identified several conditions under which at least one species from each of the three functional groups-producers, consumers, and decomposers-and one functionally redundant species, persisted for over six months. These conditions set the stage for detailed investigations in the future. Given its designability and experimental replicability, our model ecosystem offers a promising platform for deeper insights integrating both population and ecosystem dynamics.

Troubles and hardships faced by psychologists in cancer care.

OBJECTIVE: The aim of this study was to identify problems experienced by psychologists involved in cancer and palliative care and consider an education system for psychologists. METHODS: We conducted a questionnaire survey of psychologists involved in cancer care and palliative care. At the 403 facilities, 419 psychologists who received the questionnaire were asked to fill it out anonymously. A total of 294 people (61 male, 233 female, average age ± SD = 36.3 ± 9.4) responded about troubles and hardships actually faced by psychologists working in cancer care. We performed qualitative content analysis of free responses. RESULTS: We obtained the following five categories: 'Hospital system', 'Psychologist role and specialization (ambiguity of the role expected of psychologists and problems arising because psychologists are not nationally licensed)', 'Collaboration with other medical professionals (problems with the method of requesting psychologist cooperation and problems of consultation and liaison work within the hospital)', 'Specialized support provided by psychologists (difficulty of interaction with patients and their families, inadequate provision of psychological support in cancer care, problems related to death care and lack of psychiatric knowledge)', 'Stress faced by psychologists (psychologist's isolation and anxiety, psychologist's internal conflicts, psychologist burnout and helplessness and psychologist self-improvement)'. CONCLUSIONS: Psychologists must acquire at least a minimal level of medical knowledge and understanding of cancer treatment. Furthermore, they require training through specific case studies in order to facilitate collaboration with other medical professionals and concrete training in aspects of psychological support that are specifically tailored to cancer treatment through case studies.

[Marked reactive plasmacytosis accompanied by drug eruption in a patient with aplastic anemia].

A 61-year-old woman with aplastic anemia was admitted to our hospital in October 2009 because of fever and abdominal pain. She had been treated with cyclosporin A without showing any effect. On admission, uterine cancer was diagnosed and the left uterine appendages were swollen. She was treated with cefepime for febrile neutropenia without effect, and left-sided adnexitis was diagnosed. After cefepime was changed to meropenem, marked plasmacytosis was observed in the peripheral blood (23%) and bone marrow (79%) with the appearance of skin eruption. Although the plasma cells were morphologically abnormal, the cytoplasmic immunoglobulin light chain deviation was not detected by flow cytometric analysis, and M protein was not found by serum immunoelectrophoresis. She was diagnosed with reactive plasmacytosis and treated with dexamethasone. The drug eruption and plasmacytosis improved soon after starting the treatment. Although reactive plasmacytosis is observed with a variety of conditions, including infection, neoplasms, autoimmune disorders, and hemolytic anemia, it has not been reported to accompany drug eruption. Reactive plasmacytosis is sometimes not possible to distinguish from plasma cell neoplasms on morphology alone and needs to be diagnosed comprehensively by using flow cytometric analysis and immunohistochemical evaluation.

Treatment of fecal impaction in children using combined polyethylene glycol and sodium picosulphate.

BACKGROUND AND AIM: Polyethylene glycol (PEG) is the gold standard for fecal disimpaction in constipation. A regimen of PEG combined with the stimulant laxative sodium picosulphate (SPS) produced fecal disimpaction in chronically constipated children in the community, but it is unknown if it is effective for more severe constipation. To determine the stool output and effect of a combined PEG and SPS regimen on fecaloma in children with severe constipation and impaction. METHODS: Children with symptoms for a duration of ≥2 years, a palpable fecaloma, and enlarged rectum on X-ray (rectal: pelvic ratio > 0.6) were recruited from a tertiary hospital. Daily diaries recorded laxative dose, stool frequency, volume, and consistency (Bristol stool scale, BSS). Abdominal X-rays were taken on day 1 and day 8, and stool loading was assessed using the Leech score. Laxative doses were based on the child's age. The dose of PEG with electrolytes taken was 2-8 sachets (14.7 g/sachet) on days 1-2, reducing to 2-6 sachets on day 3. The SPS dose was 15-20 drops on days 2-3. RESULTS: Eighty-nine children (4-18 years) produced a large volume of soft stool (median/inter-quartile-range: 2.2/1.6-3.1 L) over 7 days. Stool volume on X-rays decreased significantly in the colon (P < 0.001). Fecalomas resolved in 40 of 89 children, while 49 needed a second high dose. Rectal:pelvic ratios did not change. CONCLUSIONS: A combined high dose of PEG and SPS on days 1 and 2 was effective in removing the fecaloma in half of the children. Administering high doses for a longer period should be tested to provide outpatient disimpaction for severe fecalomas. Rectums remained flaccid after emptying.

[Acute promyelocytic leukemia associated with hemophagocytic syndrome].

A 19-year-old man was referred to our hospital with pancytopenia and disseminated intravascular coagulation (DIC). Bone marrow aspiration revealed 93.6% of atypical promyelocytes and marked hemophagocytosis by macrophages. The diagnosis of acute promyelocytic leukemia (APL) associated with hemophagocytic syndrome (HPS) was made. As there was no evidence of infection, collagen diseases, or abuse of medicine, his HPS was classified as malignancy-associated HPS (MAHS). The DIC improved after administration of idarubicin and all-trans-retinoic acid (ATRA). On the 11th day, however, DIC and elevation of serum LDH recurred with the appearance of hepatosplenomegaly. Although APL cells had decreased in the bone marrow, hemophagocytes persisted. After administration of dexamethasone and etoposide, DIC and HPS improved, and complete remission of APL was obtained. ATRA was implicated in the aggravation of APL-induced MAHS in the present case.

Atypical chronic myeloid leukemia with isochromosome (X)(p10): A case report.

Atypical chronic myeloid leukemia (aCML) is a rare subtype of myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Although recurrent chromosomal and genetic abnormalities are frequently observed in aCML, none are specific to this type of leukemia. The present study reported a case of aCML associated with i(X)(p10), a rare recurrent chromosomal abnormality of hematological malignancy. A 40-year-old female was referred to the Tokyo Medical and Dental University Hospital (Tokyo, Japan) due to slight leukocytosis and anemia. A bone marrow aspiration revealed 4% blasts and granulocytic hyperplasia with dysplasia. A G-banded cytogenetic analysis of the bone marrow cells revealed 46, X, isochromosome X(iX)(p10) in all metaphases. The percentage of the neutrophil precursors promyelocytes, myelocytes and metamyelocytes in the peripheral blood was >10% throughout the clinical course of the patient, which resulted in a diagnosis of atypical chronic myeloid leukemia. Treatment with hydroxycarbamide was not able to effectively alleviate leukocytosis, and the disease progressed with the appearance of an additional cytogenetic abnormality, t(10;17)(p13;q21). Subsequently, the patient underwent allogeneic stem cell transplantation from a sibling donor, and subsequent cytogenetic analysis revealed a normal karyotype with full donor chimerism. The isodicentric X(idicX)(q13) mutation is a similar abnormality to i(X)(p10) and may result in a loss of the X-inactive specific transcript gene located at Xq13.2, the deletion of which has been previously reported to result in the development of MDS/MPN in mice. In addition, i(X)(p10) was identified as the sole chromosomal abnormality at the diagnosis of aCML in the case of the present study, which is similar to patients from previous studies of other hematological malignancies and supports the hypothesis that i(X)(p10) may have served a primary role in the leukemogenesis of aCML.

[Bortezomib-induced tumor lysis syndrome with a remarkable elevation of LDH in a case of relapsed and therapy-resistant multiple myeloma].

A 60-year-old female patient with a therapy-resistant Bence-Jones (BJ) lambda-type multiple myeloma was treated with bortezomib. She had been treated with tandem autologous stem cell transplantations and achieved complete remission before her disease relapsed. Sixteen hours after the first administration of bortezomib, an episode of fever, slight consciousness disturbance and vomiting occurred, which was accompanied by a remarkable elevation of LDH (3608 IU/l). Serum levels of creatinine, uric acid, and AST were also transiently elevated. Serum interleukin-6 level was also increased after the administration of bortezomib. The symptoms disappeared rapidly within 48 hours. Bortezomib at a 25%-reduced dose was administered again along with dexamethasone 26 days later, which caused a moderate increase in LDH levels, but no other symptoms. Further treatment caused no increase in LDH. The treatment was very effective and eradicated both urinary BJ protein and bone marrow myeloma cells after 8 sessions of bortezomib administration. These findings suggest that a bortezomib-induced rapid reduction in tumor burden led to tumor lysis syndrome, for which caution is needed when treating myeloma patients with this very effective agent.

[Ischemic colitis following the treatment of acute hemorrhage in a patient with acquired hemophilia A].

A 66-year-old man with hypertension and hyperlipidemia developed a hemorrhagic stomal ulcer and massive hematoma of the face at 4 and 7 months, respectively, after fundusectomy for early gastric cancer. The diagnosis of acquired hemophilia A was made based on the marked prolongation of activated partial thromboplastin time, an extremely low factor VIII activity, and a very high-titer factor VIII inhibitor. After admission, oral prednisolone and cyclophosphamide were started. In addition, activated prothrombin complex concentrates and recombinant activated factor VII were intravenously administered which successfully controlled his hemorrhage. Only 1 week after the episode of bleeding, however, he complained of abdominal pain accompanied by watery stool with fresh blood. The diagnosis of ischemic colitis was made based on the clinical course and the findings on both CT-scan and colon fiberoscopy. The colitis spontaneously and quickly resolved with conservative observation. To the best of our knowledge, this is the first reported case of ischemic colitis that occurred in an acquired hemophilia patient without simultaneous administration of coagulation factors or antifibrinolytic agents. We should thus pay attention to the possible occurrence of thrombotic events even in acquired hemophilia patients in the presence of risk factors for thrombosis.

Diverse effects of the Notch ligands Jagged1 and Delta1 on the growth and differentiation of primary acute myeloblastic leukemia cells.

OBJECTIVE: Notch signaling plays a role in regulating the self-renewal and differentiation of hematopoietic progenitors. Since acute myeloblastic leukemia (AML) originates from dysregulated hematopoietic progenitors, the Notch system may be involved in the abnormal growth. We previously reported that AML cells express Notch proteins. In this study, we examined the effects of recombinant human Notch ligand proteins, Jagged1 and Delta1, on the growth and differentiation of primary AML cells. MATERIALS AND METHODS: AML cells separated from blood from 12 patients were cultured in wells coated with Jagged1, Delta1, or control IgG. The short-term growth was evaluated using a colorimetric assay. The self-renewal capacity was evaluated by the clonogenic cells recovered, which were obtained via a colony assay involving cells cultured with the ligands or control IgG. Differentiation was evaluated by the morphology of the cultured cells and flow cytometric analysis. RESULTS: The ligand stimulation caused three types of response in the short-term growth of the primary AML cells, namely, promotion, suppression, or no significant effect. The self-renewal capacity was suppressed or not significantly affected by the ligands, even in cells showing short-term growth promotion. The ligand stimulation altered blast cells into macrophage-like cells from their morphology and increased the expression of differentiation markers such as CD13 or CD14 in some samples. CONCLUSIONS: The Notch ligands had diverse effects on the short-term growth of primary AML cells. The ligands did not promote the self-renewal capacity of any of the cells examined and instead tended to induce differentiation under the conditions used.

Clonal evolution with inv(11)(p15q22) and NUP98/DDX10 fusion gene in imatinib-resistant chronic myelogenous leukemia.

The BCR/ABL tyrosine kinase inhibitor imatinib has shown remarkable efficacy in treating patients with chronic myelogenous leukemia (CML). In a small portion of patients treated with imatinib, however, the disease may progress to advanced stages, frequently accompanied by cytogenetic clonal evolution with the appearance of additional chromosomal aberrations besides the Philadelphia chromosome. Here we report the appearance of an inv(11)(p15q22) as a clonal evolution in a CML patient undergoing treatment with imatinib. Leukemic cells from the patient were found to express the fusion transcript of NUP98 and DDX10, which is in accordance with previously reported cases of de novo or therapy-related acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(p15q22). Although the patient showed resistance to imatinib with the disease rapidly progressing to blast crisis, sequence analysis failed to reveal any mutation in the kinase domain of BCR/ABL that would explain the imatinib resistance. Furthermore, ex vivo treatment of leukemic cells with imatinib significantly reduced tyrosine phosphorylation of CrkL, a target of the BCR/ABL kinase. These observations raise a possibility that the NUP98/DDX10 fusion might be involved in imatinib resistance as well as in acute transformation of CML.

[Successful treatment with drainage of hematoma and chemotherapy in a case of Burkitt leukemia presenting with subdural hematoma].

A 53-year-old male was admitted because of pancytopenia and chronic subdural hematoma. Bone marrow was hypercellular with 97% blasts, which expressed CD10, CD19, CD20, and immunoglobulin mu and gamma chains on the cell surface and had chromosomal abnormalities including t(8 ; 22)(q24 ; q11). The patient was diagnosed as having Burkitt leukemia. Because hemiplegia and disturbance of consciousness developed rapidly, the patient was treated with an emergency drainage operation followed by Hyper-CVAD therapy and achieved a sustained complete remission. Dural infiltration of leukemic cells as well as thrombocytopenia was implicated in the pathogenesis of the subdural hematoma, which contained numerous blasts.

Therapy-related leukemia with Inv(16)(p13.1q22) and type D CBFB/MYH11 developing after exposure to irinotecan-containing chemoradiotherapy.

A 40-year-old woman developed therapy-related acute myeloid leukemia (t-AML) with inv(16)(p13.1q22) and a rare type D form of core-binding factor ß-subunit gene-myosin heavy chain 11 gene (CBFB-MYH11) fusion transcript approximately 2.5 years after receiving chemoradiotherapy for uterine cervical cancer. t-AML with inv(16)(p13.1q22) and rare non-type A CBFB-MYH11 typically develops after exposure to a topoisomerase II inhibitor, with a short period of latency of one to five years. As the patient had no history of exposure to topoisomerase II inhibitors, among her previously used chemotherapeutics, the topoisomerase I inhibitor, irinotecan, was speculated to be the most plausible cause of t-AML in this case. The present case suggests that irinotecan may cause t-AML resembling that associated with topoisomerase II inhibitors.

Secondary near-tetraploidy with double der(15)t(15;17) in acute promyelocytic leukemia in relapse.

Tetraploidy or near-tetraploidy is a rare cytogenetic abnormality in acute myelocytic leukemia. We report here a case of acute promyelocytic leukemia that showed near-tetraploidy with double der(15)t(15;17) the leukemia relapsed. At diagnosis, cytogenetic analysis failed to reveal any karyotypic abnormality; however, a promyelocytic leukemia-retinoic acid receptor alpha (PML/RARA) fusion transcript of the bcr3-type was detected with reverse transcriptase-polymerase chain reaction analysis, and a single PML/RARA fusion signal was observed with fluorescence in situ hybridization analysis. At the first relapse, the majority of leukemic cells showed pseudodiploid karyotypes with der(15)t(15;17), as well as additional chromosomal abnormalities, and exhibited a single PML/RARA fusion signal. A small fraction of leukemic cells, however, showed near-tetraploid karyotypes with double der(15)t(15;17), as well as some additional chromosomal abnormalities in common with the pseudodiploid clones, and exhibited double PML/RARA fusion signals. At the second and third relapses, leukemic cells with near-tetraploidy and double PML/RARA fusion signals became predominant. The PML/RARA fusion transcript of the bcr3 type was also observed at each relapse. In addition, Southern blot analysis of the RARA gene at diagnosis and at the second relapse showed a common rearranged band. Notably, giant, bizarre, and hypogranular promyelocytes expressing CD2, CD34, and HLA-DR appeared at the first relapse and became predominant at the second and third relapses. These observations indicate that the APL cells with near-tetraploidy and double der(15)t(15;17) clonally evolved from the pseudodiploid leukemic cells and exhibited the bizarre morphology and aberrant surface immunophenotypes.

[Hypercalcemia mediated by parathyroid hormone-related protein in the blastic phase of chronic myelogenous leukemia].

A 45-year-old man with chronic myelogenous leukemia (CML) in the accelerated phase was admitted to our hospital because of lower back pain and hypercalcemia. On admission, he was confused and found to have massive splenomegaly. The hypercalcemia and splenomegaly improved significantly after administration of incadronate, hydroxyurea, vincristine and prednisolone. Splenomegaly recurred after cessation of the chemotherapy, and examination of the peripheral blood showed 31% blasts, positive for both CD13 and CD33, on which basis myeloid blastic transformation was diagnosed. Vindesine, cytarabine and prednisolone were administered, and the splenomegaly improved again. On admission, when the patient's serum calcium level was 16.0 mg/dl, his serum parathyroid hormone-related protein (PTHrP) level was elevated to 118.3 pmol/l. Furthermore, RT-PCR analysis revealed that the patient's CML cells expressed PTHrP mRNA, and a high level of PTHrP was detected in the supernatant of cultured mononuclear cells derived from the patient's peripheral blood. These findings indicated that the hypercalcemia was due to production of PTHrP by the leukemic cells. Several cases of PTHrP. mediated hypercalcemia associated with CML have been reported previously, and are reviewed here.

[Late appearance of Philadelphia chromosome with the p190 BCR/ABL chimeric transcript in acute myelogenous leukemia progressing from myelodysplastic syndrome].

We report a late appearance of the Philadelphia chromosome (Ph) with the p190 BCR/ABL chimeric transcript in a 69-year-old patient with acute myelogenous leukemia (AML) that had evolved from myelodysplastic syndrome (MDS). In July 1997, the patient was found to have pancytopenia caused by refractory anemia with excess of blasts, which evolved into AML in 4 months. The leukemic cells were positive for CD13, CD14, CD33, and HLA-DR and had a normal karyotype. The patient achieved a complete remission after combination chemotherapy. However, his leukemia relapsed in November 1999, with the appearance of leukemic cells positive for CD7, CD13, CD34, and HLA-DR with a 46, XY, add (18) (p11) karyotype. The patient failed to achieve the second remission after several courses of intensive chemotherapy. When the number of blastic cells, showing the same surface phenotypes, in the peripheral blood increased drastically in April 2000, chromosomal analysis of leukemic cells revealed a 46, XY, t(9;22) (q34;q11), add(18)(p11) karyotype. The fusion of the BCR and ABL genes was confirmed by fluorescence in situ hybridization analysis, and the reverse transcription-polymerase chain reaction analysis further revealed the presence of the p190 BCR/ABL chimeric transcript. The appearance of the Ph chromosome in the course of MDS transforming to AML is very rare and may be correlated to the disease progression.

Loss of function of the IAA-glucose hydrolase gene TGW6 enhances rice grain weight and increases yield.

Increases in the yield of rice, a staple crop for more than half of the global population, are imperative to support rapid population growth. Grain weight is a major determining factor of yield. Here, we report the cloning and functional analysis of THOUSAND-GRAIN WEIGHT 6 (TGW6), a gene from the Indian landrace rice Kasalath. TGW6 encodes a novel protein with indole-3-acetic acid (IAA)-glucose hydrolase activity. In sink organs, the Nipponbare tgw6 allele affects the timing of the transition from the syncytial to the cellular phase by controlling IAA supply and limiting cell number and grain length. Most notably, loss of function of the Kasalath allele enhances grain weight through pleiotropic effects on source organs and leads to significant yield increases. Our findings suggest that TGW6 may be useful for further improvements in yield characteristics in most cultivars.

Sequential monitoring of serum IL-6, TNF-α, and IFN-γ levels in a CAEBV patient treated by plasma exchange and immunochemotherapy.

We report the case of a female patient with chronic active Epstein-Barr virus infection (CAEBV) accompanied by hemophagocytic syndrome (HPS). On admission, she presented with severe liver dysfunction and disseminated intravascular coagulation with elevation of serum IL-6, TNF-α, and IFN-γ levels. Plasma exchange (PE) followed by immunochemotherapy with prednisolone, cyclosporine A, and VP16 was performed. PE decreased serum cytokine levels dramatically and improved liver function. Following immunochemotherapy, CAEBV became inactive. Four months after discharge, however, CAEBV relapsed with HPS, and serum cytokine levels were extremely elevated again. There was no response to immunochemotherapy, and the patient died 1 day after admission. We examined the cytokines in five additional untreated-CAEBV patients and determined that they were elevated above the normal level in all patients. These results suggest that inflammatory cytokines may have roles in the development of CAEBV, and that their depletion can be an effective treatment for this disease.