Home transfusions are implemented using diverse approaches in Japan.

BACKGROUND AND OBJECTIVES: Japan's ageing society has increased the need for home healthcare, including home transfusions. We hence aimed to elucidate the purpose and utilization of home transfusions in Japan, which has not been clarified to date. MATERIALS AND METHODS: Clinics throughout Japan that provide home care and have experience in performing blood transfusions were surveyed. The study period was February to December 2019, and information of patients receiving home red blood cell transfusions, including patient background, pre-transfusion laboratory data and the purpose of the transfusions, was collected. RESULTS: Haematological malignancies and solid tumours accounted for 70% of the patients' underlying diseases, with the former being significantly more common in urban areas. Regarding the purpose of the home transfusions, haematologists focused on symptom improvement, whereas gastroenterology surgeons focused on life support. Furthermore, maintenance of life was more likely to be the aim in the group of patients with the lowest level of activities of daily living. The main items that were significantly associated with a low haemoglobin level before transfusion included age ≥90 years and a gastroenterologist being the physician in charge. CONCLUSION: Home transfusions were found to be performed in a restrictive and diverse manner in Japan. Life support is the second most common purpose of home transfusion in Japan, and optimizing effective home transfusion remains a challenge.

Management system of home transfusion in Japan: A nationwide survey in 2019.

BACKGROUND AND OBJECTIVES: In Japan, there are various opinions on the pros and cons of home transfusion because of safety concerns. We hence aimed to elucidate the safety and availability of home transfusion in Japan, which has not been clarified to date. MATERIALS AND METHODS: Clinics throughout Japan that provide home care and have experience in performing blood transfusions were surveyed. The analysis period was February to December 2019. Basic information about the clinics, their collaboration system with core hospitals, storage method of red blood cells (RBCs) and the system for the management of patient information regarding transfusion reactions were investigated. RESULTS: Detailed information was obtained regarding the implementation of home transfusions by 51 clinics. The proportion of home care clinics performing home transfusions was 17.6%, and they were more frequently performed in urban regions. Approximately half of the clinics collaborated with a core hospital for emergency responses to transfusion reactions. At 84% of the clinics, RBC units were stored in refrigerators that were not exclusively allocated to blood storage. Nurses and family members were involved as patient attendants in 83% and 77% of the home transfusions, respectively. No serious transfusion reactions were reported among the 150 patients in 2019, nor the 623 patients up to 2018. CONCLUSION: From data on its availability and safety, home transfusions are considered to be in the developing phase in Japan. Increased cooperation between hospitals and clinics is crucial towards improving the home transfusion system in Japan in the future.

A Case of Acquired Hemophilia A: Usefulness of Various Methods for Judging Mixing Test Results for Monitoring the Effect of Immunosuppressive Therapy.

BACKGROUND: Measurement of FVIII inhibitor (FVIII INH) levels is important for determining the effect of immunosuppressive therapy on acquired hemophilia A (AHA). However, FVIII INH can only be measured at a limited number of laboratories, which means that there are delays in obtaining the results at many sites. METHODS: A series of mixing tests were carried out in a case of AHA, followed by comparison of various methods for judging the obtained results in association with a change of FVIII INH. The mixing test results were judged using the visual waveform pattern method and the index of circulating anticoagulant (ICA), as well as the difference between the APTT values of delayed-type and immediate-type waveforms (APTT D-I) as a numerical index. RESULTS: All examined judgment methods reflected the change in FVIII INH, but ICA and APTT D-I were particularly sensitive for capturing this. CONCLUSIONS: Our results suggest that a series of mixing tests are useful for rapid monitoring of the effect of immunosuppressive therapy on AHA.

Optimal prewarming conditions for Rh antibody testing.

BACKGROUND: Although prewarming (PW) can reduce the confounding agglutination of cold-reactive antibodies when testing for warm-reactive antibodies, PW also can adversely affect the detection of warm-reactive antibodies. This study was conducted to determine PW conditions that optimized Rh antibody detection. STUDY DESIGN AND METHODS: In 38 plasma samples with Rh system antibodies detected by any of four methods, and in 8 other samples with cold-reactive antibodies, reactivity was assessed by titer and score. RESULTS: PW to 37 degrees C often reduced reaction scores by all methods especially the low-ionic-strength saline indirect antiglobulin test and bromelin methods. In analyses warming red blood cell (RBC) suspensions or plasma, the reaction scores were decreased only when the RBC suspension was warmed, suggesting that RBC PW decreased Rh antibody reactivity. The warming period ranging from 5 to 30 minutes all decreased Rh system reaction scores, an effect persisting up to 120 minutes. At lower temperatures (27, 30, and 33 degrees C), numbers of samples showing decreased reaction score for Rh system antibodies decreased in a temperature-dependent manner. Testing at 27 degrees C also permitted some agglutination involving cold-reactive antibodies, whereas higher temperatures successfully suppressed their agglutination. CONCLUSION: PW at 30 degrees C minimizes problems in accurately detecting Rh system antibodies.

Survivin enhances telomerase activity via up-regulation of specificity protein 1- and c-Myc-mediated human telomerase reverse transcriptase gene transcription.

Suppression of apoptosis is thought to contribute to carcinogenesis. Survivin, a member of the inhibitor-of-apoptosis family, blocks apoptotic signaling activated by various cellular stresses. Since elevated expression of survivin observed in human cancers of varied origin was associated with poor patient survival, survivin has attracted growing attention as a potential target for cancer treatment. Immortalization of cells also is required for carcinogenesis; telomere length maintenance by telomerase is required for cancer cells to proliferate indefinitely. Yet how cancer cells activate telomerase remains unclear. We therefore examined possible interrelationships between survivin expression and telomerase activity. Correlation between survivin and human telomerase reverse transcriptase (hTERT) expression was observed in colon cancer tissues, and overexpression of survivin enhanced telomerase activity by up-regulation of hTERT expression in LS180 human colon cancer cells. DNA-binding activities of specificity protein 1 (Sp1) and c-Myc to the hTERT core promoter were increased in survivin gene transfectant cells. Phosphorylation of Sp1 and c-Myc at serine and threonine residues was enhanced by survivin, while total amounts of these proteins were unchanged. Further, "knockdown" of survivin by a small inhibitory RNA decreased Sp1 and c-Myc phosphorylation. Thus survivin participates not only in inhibition of apoptosis, but also in prolonging cellular lifespan.

Survivin enhances Fas ligand expression via up-regulation of specificity protein 1-mediated gene transcription in colon cancer cells.

Cancer cells are thought to possess mechanisms for evading the host's immune surveillance system. Survivin, a member of the inhibitor-of-apoptosis family overexpressed by cancer cells, inhibits Fas-mediated apoptosis induced by immune cells. In addition, cancer cells express Fas ligand (FasL) on their surfaces as a counterattack against immune cells. Mechanisms by which cancer cells express FasL, including involvement of survivin, are unclear. In the present study, we demonstrated that survivin up-regulated FasL expression and investigated how this might occur. Quantitative immunostaining showed correlation between survivin and FasL protein expression in colon cancer tissues (r=0.79). FasL expression was up-regulated in LS180 colon cancer cells transfected with the survivin gene. Transfectants showed increased cytotoxicity against a Fas-sensitive human T leukemia cell line, Jurkat. In contrast, FasL expression was down-regulated in SW480 cells transfected with a small inhibitory RNA to prevent survivin expression. Survivin gene transfectants showed increased DNA binding of transcription factor specificity protein 1 (Sp1) to the FasL promoter, and up-regulation of Sp1 phosphorylation at serine and threonine residues; the total amount of Sp1 was unchanged. Thus, survivin enables cancer cells not only to suppress immune cell attack by inhibiting Fas-mediated apoptotic signaling, but to attack immune cells by induction of FasL.

A novel gene containing PDZ and LIM domains, PCD1, is overexpressed in human colorectal cancer.

BACKGROUND: The process of colorectal cancer development involves accumulated genetic alterations affecting APC, K-ras and p53. A recently identified gene, PCD1, was reported to be up-regulated in human malignancies including colorectal cancers, but relationships between PCD1 gene expression and clinicopathological findings, as well as the timing of genetic alteration of PCD1 in colorectal cancer development, are not clear. To determine whether PCD1 contributes to colorectal cancer progression, we investigated the expression of PCD1 mRNA in human colorectal tissues. MATERIALS AND METHODS: The expression of PCD1 mRNA was determined by quantitative RT-PCR. The mutation of p53 was detected by a PCR-SSCP method. RESULTS: Up-regulation of PCD1 gene transcription was observed not in adenomas but in cancers compared to normal mucosa (p < 0.0001). Primary tumors with a mutation of p53 showed significantly greater PCD1 gene expression than tumors without such a mutation (p = 0.0134). CONCLUSION: The PCD1 gene may play a role in colorectal cancer development from adenomas.