Quantitative analysis of crystallinity in an argyrodite sulfide-based solid electrolyte synthesized via solution processing

Liquid-phase synthesis is a useful technique for preparing argyrodite sulfide-based solid electrolytes, and the synthesis conditions such as heat treatment strongly affect the conductivity. Because the understanding of structural changes reveals crucial information about their properties, it is necessary to evaluate this change during heat treatment to determine the factors that affect the conductivity. In this study, X-ray diffraction measurements and transmission electron microscope observations reveal the effects of heat treatment on the crystallinities and ionic conductivities in the synthesis process of argyrodite electrolytes with tetrahydrofuran and ethanol. The amorphous material is in the main phase when heated at low temperatures below 200 °C and exhibits relatively low conductivities of ca. 2 × 10⁻⁴ S cm⁻¹ despite precipitation of the argyrodite crystals. As the heat treatment temperature increases, the ratio of argyrodite crystals increases, involving nucleation and grain growth, leading to high conductivities of over 10⁻³ S cm⁻¹. It is critical to control the ratio of the amorphous and crystal phases to achieve high conductivities in the synthesis of argyrodite electrolytes via liquid-phase processing.

Liquid-phase synthesis is a useful technique for preparing argyrodite sulfide-based solid electrolytes, and the synthesis conditions such as heat treatment strongly affect the conductivity.     

Prognostic biomarkers in patients with localized natural killer/T‐cell lymphoma treated with concurrent chemoradiotherapy

Concurrent chemoradiotherapy has become one of the standard management approaches for newly diagnosed localized nasal natural killer (NK)/T‐cell lymphoma (NKTCL). Few data are available on the prognostic biomarkers of NKTCL among patients treated with concurrent chemoradiotherapy. To evaluate the prognostic significance of immunophenotypic biomarkers for patients treated with concurrent chemoradiotherapy, latent membrane protein 1 (LMP1), cutaneous lymphocyte antigen (CLA) and cell origin were examined in samples from 32 patients who were enrolled in the Japan Clinical Oncology Group 0211 trial and treated with concurrent chemoradiotherapy. LMP1 and CLA were positive in 66% (19/29) and 29% (9/31) of the cases examined, respectively. The median follow‐up duration was 68 months (range, 61–94). The patients with LMP1‐positive tumors showed a better overall survival (OS) than the patients with LMP1‐negative tumors (hazard ratio, 0.240; 95% confidence interval [CI], 0.057–1.013; 80% CI, 0.093–0.615; P = 0.035). All five patients with LMP1‐negative tumors who experienced disease progression died of lymphoma, and both patients with local failure had LMP1‐negative tumors. There was no significant difference in OS according to CLA expression. A total of 27 (84%) cases were of NK‐cell origin, two were of αβ T‐cell origin and three were of γδ T‐cell origin. In contrast to those with tumors of NK‐cell origin, all five patients with NKTCL of T‐cell origin were alive without relapse at the last follow up. Our results indicate that LMP1 expression is a favorable prognostic marker and suggest that a T‐cell origin of the tumor may be a favorable prognostic marker for patients with localized NKTCL treated with concurrent chemoradiotherapy.     

A case of adult T cell leukemia complicated by proliferative synovitis

A 60-year-old woman was admitted to our hospital with symmetrical arthritis of the knees. During the 2 years preceding admission, she had experienced recurrent arthritis. A histological examination of her synovial tissue showed prominent villous proliferation of the synovial cells, prominent vascularity throughout and an inflammatory infiltrate composed of abnormal mononuclear cells. Three months later, she developed fever, skin eruptions, lymphadenopathy and hepatosplenomegaly. She also had hypercalcemia and there was abnormal lymphocytosis in her blood smears. She was diagnosed as having adult T cell leukemia. Parenteral chemotherapy treatment with adriamycin and cyclophosphamide gave remission of all the manifestations of disease, including arthritis. Her leukemia recurred, however, and she died 6 months after the diagnosis was made.     

Phase II study of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) therapy for newly diagnosed patients with low- and low–intermediate risk, aggressive non-Hodgkin’s lymphoma: final results of the Japan Clinical Oncology Group Study, JCOG9508

The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone, known as CHOP therapy, has been established as the standard treatment for aggressive non-Hodgkin's lymphoma (NHL). Although patients categorized as low (L) and low-intermediate (L-I) risk using the International Prognostic Index have favorable prognoses in Western countries, the efficacy and safety of CHOP therapy has not been prospectively evaluated in Japan. We conducted a phase II study of CHOP in L and L-I risk Japanese patients, evaluating overall survival (OS) as the primary endpoint. A total of 213 patients were enrolled and treated with eight courses of CHOP. Efficacy was evaluated in 168 eligible patients (L risk, 87; L-I risk, 81). Five-year OS rates in all eligible, L, and L-I risk patients were 68?% [95?% confidence interval (CI): 61-76?%], 73?% (95?% CI: 63-82?%), and 64?% (95?% CI: 53-74?%), respectively. The major toxicity observed was grade 4 neutropenia (64?%). Grade 4 non-hematological toxicities were observed as follows: one case each of paralytic ileus, convulsions, hypoxemia due to interstitial pneumonia, and reactivated fulminant hepatitis B. These results show reasonable efficacy and safety of the CHOP regimen in Japanese patients with lower risk aggressive NHL (UMIN-CTR Number C000000053).     

Giant cadherins Fat and Dachsous self-bend to organize properly spaced intercellular junctions

The cadherins Fat and Dachsous regulate cell polarity and proliferation via their heterophilic interactions at intercellular junctions. Their ectodomains are unusually large because of repetitive extracellular cadherin (EC) domains, which raises the question of how they fit in regular intercellular spaces. Cadherins typically exhibit a linear topology through the binding of Ca²⁺ to the linker between the EC domains. Our electron-microscopic observations of mammalian Fat4 and Dachsous1 ectodomains, however, revealed that, although their N-terminal regions exhibit a linear configuration, the C-terminal regions are kinked with multiple hairpin-like bends. Notably, certain EC–EC linkers in Fat4 and Dachsous1 lost Ca²⁺-binding amino acids. When such non–Ca²⁺-binding linkers were substituted for a normal linker in E-cadherin, the mutant E-cadherins deformed more extensively than the wild-type molecule. To simulate cadherin structures with non–Ca²⁺-binding linkers, we used an elastic network model and confirmed that bent configurations can be generated by deformation of non–Ca²⁺-binding linkers. These findings suggest that Fat and Dachsous self-bend due to the loss of Ca²⁺-binding amino acids from specific EC–EC linkers, and can therefore adapt to confined spaces.Cell–cell adhesion is achieved through interactions between adhesion receptors, by either homophilic or heterophilic binding with partner molecules. Cadherins are a group of cell–cell adhesion receptors, and the so-called “classical” cadherins are important for general cell–cell adhesion (1). The extracellular domain (ectodomain) of the classical cadherins is divided into five repetitive domains called extracellular cadherin (EC) domains, which are linked by a region containing a unique amino acid sequence called the Ca²⁺-binding motif (CBM) (2, 3). Binding of Ca²⁺ to this linker region confers a strand-like morphology on the cadherin molecules, which represents their active form, and this morphology breaks down when Ca²⁺ is depleted (4–6). The homophilic interactions via the N-terminal EC domains between classic cadherins result in the formation of adherens junctions (AJs), which span intercellular spaces that are ∼20 nm across (2, 3, 7).The EC domains are conserved in many other molecules grouped under the cadherin superfamily (8). These include desmosomal cadherins, protocadherins, Flamingo/Celsr, Fat, and Dachsous. Curiously, the number of EC domains among these molecules is varied, ranging from 5 to 34. This variation might be related to the functional diversity of cadherin superfamily members. For example, cadherin-23 and protocadherin-15 have 27 and 11 EC domains, respectively, resulting in their large size. Their heterophilic complex organizes the “tip link” to connect a pair of stereocilia (9). The linearly extended configuration of this complex matches the 150- to 200-nm dimensions of the tip links. The size of a cadherin molecule, however, does not always correlate with the size of the intercellular space that holds it. “Fat” is ranked as the largest cadherin molecule among the cadherin superfamily members, with 34 EC domains. It regulates planar cell polarity and cell proliferation via its heterophilic interaction with “Dachsous,” another giant cadherin with 27 EC domains (10–12). Despite their large sizes, the mammalian Fat4 and Dachsous1 have been detected in intercellular spaces that are structurally contiguous to AJs (13). Likewise, mammalian Fat1 localizes at intercellular junctions with a 30- to 45-nm gap (only twice as wide as the AJs) to form glomerular slit diaphragms (14, 15). We questioned which mechanisms allow these large molecules to fit in relatively narrow spaces. Our present studies show that, in contrast with many other cadherins, Fat4 and Dachsous1 cadherins bend at multiple sites of the molecule, so as to adapt to narrow intercellular spaces, and this bending is induced by a loss of Ca²⁺-binding amino acids in certain EC–EC linkers.     

Prognostic significance of the proportion of Ki-67-positive cells in adult T-cell leukemia

The authors examined peripheral blood samples from patients with adult T-cell leukemia (ATL) using the monoclonal antibody Ki-67 which detects a nuclear antigen present in actively proliferating cells. In patients with chronic ATL, the percentage of Ki-67-positive cells was significantly lower than in acute ATL patients (median values, 3.3% versus 18.9%, P less than 0.001). Furthermore, there was a significant inverse correlation between the percentage of Ki-67-positive cells and the length of survival (P less than 0.001). Serum lactic dehydrogenase (LDH) levels also showed a significant inverse correlation with survival, but this was less strong than that for Ki-67 (0.01 less than P less than 0.02). Thus, Ki-67 positivity appears to indicate the aggressiveness of ATL, and can possibly be used for the clinical classification of ATL patients as well as for the prediction of prognosis.     

Changes in Negative Symptoms of Schizophrenic Patients Two Years Later†

Abstract: This study investigated the course of negative symptoms by examining the psychiatric symptoms of 59 new schizophrenic patients at the first consultation and again two years later using a structured interview–the Present State Examination. An examination of the total score of the nine negative symptoms, included in the “Chronic Schizophrenic Syndrome” by Wing, showed that 27 out of the 59 patients (45.8%) had lower symptom scores two years later than they did at the first consultation (“negative symptom improvement” group), while 20 patients (33.9%) had higher scores two years after the first consultation (“negative symptom deterioration” group). There were 12% more patients in the improvement group than in the deterioration group. No significant differences were observed between the “improvement group” and “deterioration group” in relation to the following factors–subclassification of schizophrenia, mode of onset, age at the first consultation, marital status at the time of onset, academic history, employment status prior to the onset, the history of hospitalization after the onset and maintenance therapy of neuroleptics. In relation to psychiatric symptoms at the first consultation, the patients in the “improvement group” had a variety of symptoms compared to the patients in the “deterioration group,” and the presence of “incoherence of thought,”“delusion of reference” and “special features of depression” was significantly higher in the improvement group than in the deterioration group.     

Symptoms and social adjustment of schizophrenic patients as evaluated by their family members: a cross-cultural psychiatric study between offshore islands and an urban city.

We conducted a comparative study of symptoms and social adjustment of schizophrenic patients on offshore islands and one urban region in Japan. In the evaluation of symptoms and social behavior by family members, no differences were observed between the two regions. Looking at social adjustment in the two regions, no differences were observed by family members either in the performance level or in the expectation level of socially expected activities. However, on the offshore islands, the expectation level of socially expected activities by family members was significantly higher than the level of self-accomplishment set by schizophrenic patients themselves. As for leisure activities, both family members and patients on the islands evaluated the level of performance to be significantly higher than in the urban region, and the level of satisfaction of the patients themselves was also higher on the islands. Considering both these findings and Japanese traditional views of work and leisure, it is believed that on the islands patients are required to engage in more productive activities and less leisure activities than in the urban region. Further it seems that patients on the islands compared to patients in the urban region may have greater difficulty in social adjustment.