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What is known and objective 5-Azacitidine (AZA) is an agent widely used to treat myelodysplastic syndrome (MDS). Case description We herein report an 83-year-old woman diagnosed with MDS who was treated with AZA. She tolerated the first cycle of AZA; however, severe adverse events involving haemorrhagic enteritis with multiple intestinal ulcers developed after the second and third cycles. Additionally, the interval between the administration of AZA and the development of haematochezia shortened with each cycle of AZA. What is new and conclusion We herein report as-yet-undescribed potential side effects, AZA-associated haemorrhagic enteritis that should be kept in mind.

The efficacy of 30 platelet concentrate (PC) products transfused to a patient with myelodysplastic syndrome (MDS) was evaluated by calculating the 1-hour post-transfusion corrected count increment (1h-CCI). Of the 30 transfusions, all HLA-A/B-matched, the cross-match (CM) test was negative in 23 (CM(-)-PC) and weakly positive (CM(+)-PC) in 2, and the CM test was not conducted in 5 (non-CM-PC). The effective rate was higher with CM(-)-PC compared to non-CM-PC (82.6% vs 60%), but statistical significance was not achieved, which suggested that the CM test of PC may still be a not satisfactorily effective predictor of PC refractoriness. Studies are ongoing in Japan to confirm on the importance of CM test of PC.

The measurement of corrected count increment at 1-h post-transfusion (CCI-1 h) of platelet concentrate (PC) transfusion is recommended, but in the revised Japanese Guideline (2017) it was changed to "after 10-min to 1-h", following the revision of the guidelines from Western countries. Here, we aimed to investigate on the feasibility to apply the CCI measured at 10-min or 30-min post-transfusion as the surrogate of CCI-1 h. Peripheral blood was collected at 10-min, 30-min and 1-h post-transfusion of PC and the effectiveness of the transfusion was analyzed based on the CCI. In the period from December 2017 to February 2020, 8 patients, who received multiple PC transfusion (total 208) at our institution, were analyzed. We performed the univariate analyses to examine the relationship between CCI value and the categorical variables, p-value

Mucormycosis is known to be fatal, and the diagnosis is difficult to be made. Gastrointestinal mucormycosis is rarely complicated with gastrointestinal infarction. We report a rare case of mucormycosis complicated with large intestine infarction. An 82-year-old man was admitted to our hospital, because of blastosis. A diagnosis of acute myeloid leukemia prior myelodysplastic syndrome was made. On the twentieth day of admission, bleeding developed in the airway secondary to thrombocytopenia and disseminated intravascular coagulation. He died due to respiratory failure and autopsy was carried out. The novel finding of the autopsy was large intestine infarction due to mucormycosis, although the clinical course did not show features suggesting gastrointestinal mucormycosis. A diagnosis of mucormycosis was made by autopsy. In the patients with risk factors including hematologic malignancies, we should pay attention to gastrointestinal mucormycosis.

Malakoplakia is a rare chronic inflammatory condition characterized by defective macrophage function, most of which involve the genitourinary tract, and renal parenchymal involvement is uncommon. We present a case of malakoplakia affecting renal parenchyma. A 46-year-old woman with pyrexia and jaundice was referred to our department. Abdominal enhanced CT scan revealed a left pyelonephritis with ureteral stone and bilateral renal abscesses. Despite the insertion of a left ureteral stent and administration of antibiotics, the patient showed persistent high fever and elevated CRP, and no obvious improvement in clinical and imaging data. In view of the limited effectiveness of the conservative treatment in this case, we decided to perform left nephrectomy. The diagnosis of malakoplakia was made based on the histopathological findings of von Hansemann cells and Michaelis-Guttmann bodies detected in the nephrectomy specimen. She is clinically healthy up to the present (50 months after surgery) with normal clinical indicators and CT findings.

Spontaneous crystallization of monoclonal immunoglobulins (crystalglobulin) is a rare complication of multiple myeloma. We describe a 64-year-old Japanese man with skin ulcers and renal failure associated with immunoglobulin G κ multiple myeloma. Crystallized immunoglobulin was detected in his serum at room temperature. Analysis of the patient’s crystalglobulin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry suggested that the crystallization was due to abnormal glycosylation of the immunoglobulin light chain. Treatment with thalidomide and dexamethasone improved the severe skin ulcers on the patient’s extremities and partially reversed his renal failure. This report is the first of abnormal glycosylation of immunoglobulin possibly caused by modification ofN-glycans in the light chain. We concluded that abnormal glycosylation of the immunoglobulin light chain might be the cause of the patient’s skin ulcers and renal dysfunction. cr 2007 The Japanese Society of Hematology

Background: Bone lesions in multiple myeloma (MM) have a significant impact on the quality of life of elderly patients, but they have not been extensively investigated in the elderly. Methods: The subjects were 146 elderly MM patients (aged ≥ 65 years, median age 74) admitted to 11 institutions. Bone lesions were compared with those in 65 non-elderly MM patients. Results: At the time of diagnosis, skeletal symptoms were present in 104 cases and bone pain in 75. Mixed type occurred more often in elderly patients (63.5%) than in controls (28.3%) (P

A 75-year-old woman was referred to us because of cough, high fever and skin erythema in April 1999. Malignant lymphoma (diffuse mixed cell type) was previously diagnosed in 1990 and she achieved complete remission after treatment with a series of CHOP regimen treatments. In 1998, multiple myeloma (IgG lambda type) was diagnosed and she was treated with a combination of melphalan and prednisolone. On physical examination, superficial lymphadenopathy and skin erythema were noted. Biclonal gammopathy (IgG kappa/lambda) was shown in serum, and Bence Jones protein in urine. Computed tomography showed pleural effusion and swelling of paraaortic lymph nodes. The bone marrow examination showed an increased number of abnormal plasma cells (19.2%) and no evidence of lymphoma. Left axillary lymph node biopsy revealed that she had non-Hodgkin's lymphoma (immunoblastic lymphadenopathy-like T cell lymphoma). She was treated with the CHOP regimen at reduced doses for both diseases. The lymphoadenopathy reduced after 6 courses of CHOP and 4 courses of CHOPE (CHOP + VP16), however, she had bone pain on November 1999 and received treatment with MCNU-VMP (MCNU + VDS + L-PAM + PSL). Her rib pain improved, but she died of systemic infection of herpes zoster virus. We report here a rare case of malignant lymphoma concomitant with multiple myeloma.

We have designed a protocol for ABO-incompatible kidney transplantations based on preoperative plasmapheresis with a tacrolimus/mycophenolate mofetil/methylprednisolone/basiliximab protocol using low-dose rituximab (200 mg/body) instead of splenectomy to prevent antibody-mediated acute rejection. Eight patients successfully received transplants with this protocol. The titers of anti-A and -B antibodies as well as the number of CD20 + cells were readily maintained at a low level posttransplantation. There were no side effects. All patients have renal transplant function with a follow-up of 1–34 months.

Of 43 elderly patients who were suspected to have polycythemia between October 1990 and July 1998, 12 patients showed an increased red cell volume measured by 51Cr-labeled red blood cells. We analyzed the clinical characteristics of the 12 patients consisted of 7 men and 5 women, with a median age of 71 (range: 57-92). Chief complaints were headaches and dizziness (3 cases), symptoms of other conditions than polycythemia (4 cases). Five patients had no symptoms. Five of 6 patients over 70 years old had no symptoms due to polycythemia. Seven cases (58%) showed splenomegaly and three cases (25%) showed hepatomegaly. Laboratory findings were as follows: WBC 9.7 +/- 3.9 x 10(3)/microliter (mean +/- SD, p < 0.02 vs normal control), Hb 17.9 +/- 4.2 g/dl (p < 0.001), Plt 39.7 +/- 26.0 x 10(4)/microliter, EPO 13.8 +/- 5.2 mU/ml (p < 0.0001), NAP score 258 +/- 114, Vit. B12 1,686 +/- 2,156 pg/ml, arterial O2 saturation more than 92% in all cases. The diagnosis of all cases was polycythemia vera according to the diagnostic criteria of Polycythemia Vera Study Group. Associated conditions included 8 cases of thrombosis (cerebral thrombosis 4, thrombophrebitis 2, myocardial infarction 1, ischemic colitis 1) and 3 cases of malignancy (esophageal cancer 1, breast cancer 1, renal cancer 1), none of which was therapy-related cancer. Six patients (50%) had only phlebotomy, three (25%) only chemotherapy, and three (25%) both phlebotomy and chemotherapy. Patients over 80 years old needed neither intensive nor continuous treatment. Only one patient died due to esophageal cancer at age 89.

Basiliximab is potent, relatively safe immunosuppressive induction agent used in transplantation. Prophylactic use at the time of transplantation has been advocated to improve allograft outcomes. We report two cases of kidney transplant recipients with anaphylactic reactions after initial exposure to Basiliximab.

Fifty patients, aged 60 years or more, who had been admitted to a hematology ward for more than 1 month, were studied in regard to their understanding of informed consent. The doctors informed 74% of their patients about the disease for which they were being treated. The rate of informing patients remained low in those with advanced age or with malignant tumors. However, only 42% of the patients realized that they had been informed of their diagnosis and clinical condition. The comprehension rate remained low at 43.2% even in patients who were informed by their doctors. While 60% of patients declared that they understood what the doctors described, only 36% could write something about the name or the state of their disease. Even among the patients who could understand the doctor's explanation, the comprehension rate was 43.3%. Sixty-six percent of patients demonstrated their wish to have a correct explanation of their diagnosis, 36% of patients wanted to be treated according to their own wishes, and 48% of patients left the decisions regarding their treatment to the doctors.

61歳ではじめて異常ヘモグロビン血症 (HbJ Cape Town) と診断された男性例. 3年前より検診で食後高血糖を指摘されていたが放置. 平成6年3月全身倦怠感, 食欲不振が出現し, 近医にて尿糖, 尿蛋白陽性, 肝機能異常指摘され精査目的で入院. 入院時検査にて, 空腹時血糖116mg/dl, HbA1c 22.3%, GOT 24IU/l, GPT 17IU/l, Al-P 117IU/l, LAP 42IU/l, γGTP 104IU/l, ChE 199IU/l, 75gOGTT急峻型高血糖パターンを示した. 入院後の経過では, 急峻型高血糖は胃切除によるものであり, 糖尿病は否定された. HbA1c高値の原因を調べたところ, 等電点電気泳動法で異常ヘモグロビンを陽極側に検出し, CMクロマトグラフィーでのグロビン分画ではα鎖の前に異常ピークを認めた. このα鎖グロビンを逆相-HPLCで分析したところ正常鎖でα92位に存在するアルギニン (Arg) がグルタミン (Gln) に置換されていた. この異常ヘモグロビンは血色素構造解析によってHbJ-Cape Town であることが判明した. 異常ヘモグロビン血症は, 通常若年のうちに診断されるが, 60歳以上の高齢者において初めて診断されることも稀ではないと考えられた.

Febrile episodes occurring in 29 elderly patients (mean age 75 years) with leukemia, from 1988 to 1993, were reviewed. A febrile episode was defined as a temperature of 38 degrees C or greater for at least 6 hours. The number of febrile episodes was 64. The average was 2.2 febrile episodes per patient. Seventy-two percent of febrile episodes occurred when the patients had neutropenia below 100/microliters, while 16% occurred with neutropenia of 101/microliters to 500/microliters. Causative microorganisms were identified in 48% of total febrile episodes. The most common infectious site was the urinary tract which accounted for 25% of total episodes. Pneumonia and septicemia accounted for 22% of total episodes, respectively. Gram-positive cocci were responsible for 66% of microbiologically documented febrile episodes, while 21% were caused by gram-negative bacilli. Gram-positive cocci, particularly staphylococcus aureus, coagulae-negative staphylococcus and enterococci increased compared with a decade ago in our department. Granulocyte colony-stimulating factor (G-CSF) was used 12 times for infection. No significant difference in fever amelioration was seen between G-CSF and non-G-CFS cases.

We have already reported significant elevation of serum granulocyte colony-stimulating factor (G-CSF) in the acute phase of infection. In this study, we compared the responses to infection between patients with frequently repeated infection (repeaters) and others (non-repeaters). We examined the clinical data and serum G-CSF levels in 48 patients with acute infections. Serum G-CSF levels were significantly lower in repeaters than in non-repeaters (197.7 +/- 370.0 vs. 1014.1 +/- 924.4 pg/ml. P less than 0.001). There were no significant differences in age, serum total protein, or cholinesterase between the groups, but serum albumin was significantly lower in repeaters than in non-repeaters (2.87 +/- 0.5 vs. 3.31 +/- 0.4 g/dl. P less than 0.005). It is suggested that administration of recombinant G-CSF may be useful for patients with repeated infections.

As the number of patients on hemodialysis increases, there will also be an increase in the number of patients with inadequate superficial veins for the creation of an autogenous arteriovenous fistula (AVF). In those patients, medical devices such as vascular prostheses or tunneled-cuffed catheters are necessary to maintain dialysis access. However, these devices are frequently associated with bacterial infection. We recently encountered a dialysis patient who underwent tunneled-cuffed catheter insertion because of the lack of usable superficial veins for autogenous access, and this patient subsequently developed catheter-related Staphylococcus aureus bacteremia with multiple metastatic infections. Despite immediate removal of the catheter, the infection persisted over an extended period, which was a condition precluding the further use of catheters or other prosthetic materials. To handle this situation, we utilized the deep brachial vein to construct an autogenous AVF. After ligating numerous branches, the vein was anastomosed to the brachial artery and then transposed to the subcutaneous space. The newly constructed autogenous AVF, which successfully kept the patient free from foreign materials, greatly contributed to the relief of persistent infection. Although the brachial vein is rarely used for AVF creation, we suggest that it can serve as an option to create an alternative AVF in a patient with inadequate superficial veins.

To investigate the actual situation of multiple cancers including hematological malignancies, 266 autopsy cases with one or more hematological malignancies were compiled from autopsy case files between January 1995 and October 2006 in our hospital. The median age at death was 75 years (range 48 to 102 yr). Of 266 cases, 72 (27.1%) had multiple cancers. Of these 72 cases, 62 cases were complicated with non-hematological malignancy, and 10 cases showed duplication of other hematological malignancies. Prostate and colon cancers were frequent as complicating cancers. Seventeen of 256 cases without duplication of other hematological malignancies demonstrated 3 or 4 cancers (6.6%). Of 10 cases showing duplication of other hematological malignancies, 9 cases had NHL. The rate of multiple cancers in elderly patients with hematological malignancy was higher than that of non-hematological cancers.

Autologous blood transfusion (ABT) is rarely employed in patients with end-stage renal disease (ESRD); these patients are usually anemic. Since 1998, we have attempted ABT for ESRD patients undergoing living-related kidney transplantation. Among 20 patients enrolled in this study the preoperative hemoglobin and hematocrit levels were 10.0 +/- 1.2 mg/dL (range, 8.1-11.7) and 30.0 +/- 3.7% (range, 24.7-34.3), respectively. Blood volume collected on each occasion was 235.7 +/- 57.7 mL (range, 200-400), and the number of blood collections was 2.45 +/- 0.9 (range, 1-4). Total collected volume was 567.5 +/- 157.5 mL (range, 400-800). Symptomatic hypotension was seen in two patients, but vital signs recovered spontaneously. No other problems related to blood collection were observed. Allogeneic transfusion was need in only one patient (5%). ABT was safe and efficacious in ESRD patients scheduled for living-related kidney transplantation.

A 66-year-old male was admitted to our hospital complaining of bilateral hypochondrial pain, back pain and loss of weight in May, 2002. Superficial lymph nodes were not palpable on admission. The leukocyte count was 3430/microl, hemoglobin concentration, 13.0g/dl, and platelet count, 174000/microl. LDH, soluble IL-2 receptor, ACTH and cortisol values were out of the normal range (LDH 1368IU/l, sIL-2R 2630U/ml, ACTH 132pg/ml, cortisol 7.4microg/dl). Abdominal CT scan showed bilateral adrenal masses, and abnormal uptake of Ga-scintigraphy was seen correspondent with the bilateral adrenal masses. The histological diagnosis of bilateral adrenal masses cannot be performed because of the bleeding tendency, but atypical cells were observed in the patient's bone marrow aspirate. Surface marker analysis of atypical cells showed CD5+, cyclin D1+, CD19+, CD20+ and HLA-DR+. From these results we diagnosed this case as a mantle cell lymphoma (stage IV B) markedly infiltrated into the adrenal glands with adrenal insufficiency. The bilateral adrenal masses dramatically reduced in size after CHOP chemotherapy with hydrocortisone supplementation. We report on the present case and summarize the reports of adrenal grand-infiltrating lymphomas.

In this study, we identified mutations in the von Hippel-Lindau gene (VHL) in patients with sporadic clear cell renal carcinoma and analyzed the relationship between these VHL mutations and VHL protein (pVHL) expression levels. Analysis of VHL coding region mutations by direct polymerase chain reaction in 39 patients with clear cell renal carcinoma, who had all undergone radical nephrectomy, revealed heterozygous mutations in 7 (17.9%) of the 39 patients, including 2 novel mutations. Analysis of the levels of pVHL expression in tumor tissue samples from the 7 patients with mutations by Western blot analysis demonstrated that pVHL was not expressed in 3 patients, and that 3 subjects expressed about 50%, and 1 was similar to the normal level. These results suggest that the 3 patients who did not express pVHL had both mutation and loss of heterozygosity, and that the 3 patients who expressed about 50% of the normal pVHL level had heterozygous mutations.

This report describes a case which successfully treated with rituximab against autoimmune hemolytic anemia caused by both warm autoantibodies and cold agglutinin (mixed AIHA). A 52-year-old man with malaise was referred to our hospital in December 2002. A diagnosis of mixed AIHA was made. His clinical course showed that the hemolysis was mainly caused by cold agglutinin, with a possible contribution from the warm autoantibody. He was treated with prednisolone (PSL), Cyclosporine (CyA), and cyclophosphamide (CPA). The treatment with PSL, CyA, and CPA failed to stabilize the hemolysis caused by cold exposure in the winter season. In November 2013 (winter season), rituximab therapy (375 mg/m2 weekly for four weeks) was started, and the hemolysis improved. The present case suggests that rituximab is useful against mixed AIHA. Further studies are warranted to establish the effectiveness of rituximab against mixed AIHA.

We retrospectively analyzed 126 acute myelogenous leukemia (AML) patients agedor =60 years who had all been referred to the same hematological department between 1989 and 1999. In 76 de novo AML cases, 53 patients (median age, 72 years) were treated with combination chemotherapy (CT) for remission induction. Complete remission (CR) rate was 57.1%. The median overall survival (OS) was 16 months, and the rate of 3-year OS was 28%. The favorable prognostic factors were performance statusor =2, cholinesteraseor =100 IU, and intermediate or favorable karyotype (P.01). Seventeen patients (median age, 78 years) with hypocellular bone marrow or poor general condition were treated with low-dose cytosine arabinoside (LDAraC). In these patients, the CR rate was 50% and the median OS was 11 months, with an OS estimate at 3 years of 14%. All patients with hypocellular bone marrow who received LDAraC for 21 days achieved CR. In 50 patients who developed AML following a myelodysplastic syndrome (MDS/AML), 22 patients (median age, 74 years) were treated with CT, and 14 (median age, 74 years) patients were treated with LDAraC. The CR rates were 22.7% and 21.4%, respectively, and the median OS durations were 8 months and 11 months, respectively. There were no significant factors that would indicate a good prognosis in MDS/AML patients.

A 69-year-old man visited our department of neurology with symptoms of paresthesia on the lower extremities and lumbago. Biochemical examination of serum samples showed hypercalcemia (serum concentration 15.6 mg/dl). The levels of intact parathyroid hormone (i-PTH) and 1, 25-dihydroxyvitamin D were suppressed, whereas parathyroid hormone-related peptide (PTHrP) was elevated up to 5.4 pM (normal range: below 0.6 pM). Additionally, bone survey revealed a punched-out lesion in radiological examinations of the skull. Bone marrow aspiration demonstrated many atypical plasma cells suggesting multiple myeloma. Nephrogenous cyclic adenosine monophosphate (cAMP), urinary deoxypyridinoline, plasma interleukin 6 (IL-6) and transforming growth factor β (β (TGF β) concentrations were elevated, whereas % of renal tubular reabsorption of phosphate (%TRP) was decreased. The immunohistochemical results demonstrated the expression of PTHrP in atypical plasma cells. These data indicated that hypercalcemia complicating multiple myeloma causes an elevation of renal calcium reabsorption and an increase of bone resorption mediated by PTHrP action.(Internal Medicine 39: 810-813, 2000)

A 72-year-old man was admitted for examination of dyspnea and pitting edema of the lower legs in July, 1996. His hemoglobin level was 6.9 g/dl, and myelodysplastic syndrome (MDS) was revealed by bone marrow aspiration, and frequent transfusions were needed. His renal function rapidly deteriorated in the middle of August (BUN 45 mg/dl, Cr 4.8 mg/dl) and IgA nephropathy (IgAN) with marked intestinal nephritis was disclosed by renal biopsy. In November, joint manifestations of warmth and pain, which suggested arthritis, appeared at the bilateral wrist and ankle joints. Soon after receiving prednisolone (20 mg/day), the arthritis was relieved. Renal function also improved (BUN 41 mg/dl, Cr 21 mg/dl) and frequent transfusions were no longer necessary. This is a case with various clinical manifestations of MDS, IgAN, and arthritis, and appears to be the first MDS case complicated with IgAN. A number of case reports have identified immune abnormalities in patients with MDS. Immune and bone marrow abnormalities have been reported to be involved in the pathogenesis of IgAN. Thus, MDS could be complicated by IgAN. Their pathogenetic association is discussed in this paper.

To clarify the physiologic roles of granulocyte colony-stimulating factor (G-CSF) in infectious states in vivo, we examined the serum levels of G-CSF in patients with infection. Serum samples from 24 patients in the acute stage of infection (14 men and 10 women, age 65 to 101, without hematologic disorders), as well as samples from 32 age- matched normal elderly volunteers were investigated. Sixteen of the initial 24 patients were reexamined after the recovery phase. G-CSF levels were examined by quantitative enzyme immunoassay. The G-CSF level in normal elderly controls, 25.3 +/- 19.7 pg/mL, was not different from that reported in other findings. There was no statistically significant relationship between their G-CSF level and peripheral white blood cell count or neutrophilic granulocyte count. The G-CSF level in the acute stage of infection was 731.8 +/- 895.0 pg/mL, with a range of 30 to 3,199 pg/mL. There was no significant difference in G-CSF levels between patients with respiratory tract infection and those with urinary tract infection. In all 16 cases examined, the serum G-CSF level in the acute stage of infection was significantly higher than that after recovery phase, the latter being the same as the level in normal elderly controls. G-CSF must therefore play a significant role in human infectious states in vivo.

A 79-year-old man with marked hepatosplenomegaly and lymphadenopathy was admitted to the hospital. Analysis of serum protein resulted in the diagnosis of gamma-chain disease (total protein 6.2 g/dl, M-protein positive, IgG 4150 mg/dl, IgG-Fc fragment positive). Specimens obtained by lymph node biopsies showed infiltration of plasmacytoid cells, which were stained with anti-IgG but not with anti-kappa or anti-lambda antibodies. The patient was given combination chemotherapy, but without effect. Then a regimen of long-term administration of low-dose etoposide was begun, and resulted in remission of the lymphadenopathy, hepatosplenomegaly, and abnormal IgG.

Plasma concentration of cytosine arabinoside (Ara-C) was determined in elderly patients with myelodysplastic syndromes or acute myelocytic leukemia who were treated with subcutaneous injection of Ara-C (Ara-C s.c.; 10 mg/m2/12 hr, 14-21 days), continuous drip infusion of Ara-C (Ara-C d.i.v.; 20 mg/m2/day, 24 hr 14 days) and/or oral administration of cytarabine ocfosfate (SPAC) (SPAC p.o.; 100 mg-300 mg/body/day, 14 days) by radioimmunoassay. In the Ara-C s.c. patients, the peak plasma level (Cmax) of Ara-C was 103 ng/ml and the time to reach Cmax was 15 min. The elimination half-like (t1/2) was 25 min and no accumulation was detected after 14 days of consecutive Ara-C s.c. administrations. In the SPAC p.o. patients, Cmax of Ara-C was 3-8 ng/ml and it took 3-5 days to reach Cmax. The plasma concentration level of Ara-C remains almost at the Cmax level during the SPAC p.o. administration and it remained higher than 0.32 ng/ml for as long as 15 days after the end of administration. In a Ara-C d.i.v. patient, plasma level of Ara-C was detected 4-7 ng/ml during the administration (day 7 through day 14). In all patients bone marrow suppression was observed after chemotherapy regardless of regimen, and there was no significant difference between nadir peripheral cell blood counts of Ara-C s.c. patients and SPAC p.o. patients.

Body-cavity-based lymphoma (BCBL) is a recently described subtype of human non-Hodgkin's lymphoma characterized by the localization of neoplastic cells exclusively in the body cavities. BCBL is found most commonly in AIDS patients, and is known to be highly associated with Kaposi's sarcoma-associated herpes virus (KSHV). We describe here a case of BCBL that occurred in a 101-year-old man. He was successively treated with etoposide, but died 8 months after the diagnosis of BCBL. No lymphoma masses were noted at pre- and postmortem examinations. KSHV was demonstrated in large numbers in the neoplastic cells using semiquantitative PCR analysis. Although there have been four brief reports of HIV negative BCBL, the present case is the first for which the detailed clinical course and response to chemotherapy have been recorded.

Thirty five elderly patients with acute non-lymphocytic leukemia were studied to examine the effects of antileukemic chemotherapy according to age group. Complete remissions were obtained in 5 of 10 patients (50%) age 60 to 69 years, in 5 of 14 (36%) age 70 to 79 years, but in 0 of 9 patients over 80 years. Three patients died before chemotherapy. The median survivals of these groups were 337,90 and 76 days, respectively. The median survival of the patients in whom complete remissions were achieved, was 700 days.

We investigated the genetic basis for the increased adenosine deaminase (ADA) expression in adult T-cell leukemia (ATL). We found a correlation between the levels of ADA-specific mRNA and ADA immunoreactive protein in ATL. Southern blot analysis revealed no gene amplification or rearrangement of the ADA gene. These findings indicate that increased ADA expression in ATL cells reflects increased transcriptional activity for the ADA gene or increased stability of ADA mRNA.

A new glucose-6-phosphate dehydrogenase (G6PD) variant associated with chronic nonspherocytic hemolytic anemia was reported. The patient, a 6-year-old Japanese male, was noticed to have hemolytic anemia soon after birth, and a diagnosis of G6PD deficiency was made at the age of 2. He had episodes of hemolytic crisis several times after upper respiratory infection. G6PD activity of the patient was 5.5% of normal. The enzymatic characteristics were examined when he was 5 years old, and his G6PD showed faster-than-normal electrophoretic mobility, low Km G6P, high Km NADP, low Ki NADPH, normal utilization of substrate analogues, heat instability, and a normal pH optimum curve. From these results, this was considered to be a new variant and was designated G6PD Nagano. Infection-induced hemolysis and chronic hemolytic anemia seem to be due to markedly impaired enzyme activity and thermal instability.

Pyruvate kinase (PK) has four isozymes (L, R, M1, M2) that are encoded by two different genes of PK L and M. Differential splicing produces L- and R-type PK mRNA and M1- and M2-type PK mRNA from the PK L gene and the PK M gene, respectively. The nucleotide sequences of the 3'-noncoding region are the same between the L- and the R-type PK and between the M1- and the M2-type PK. We isolated 3'-noncoding sequences of human L- and M2-type PK cDNA to construct L-type and M-type PK specific probes. With these probes, we performed Northern blot analysis of the RNA samples extracted from human tissues. Northern blot analysis showed that both kidney and liver had mRNAs that hybridized with both the L and M probes. Small intestine, skeletal muscle, brain, testis, and lung mRNAs hybridized only with the M probe. Our probes are considered useful for the detection of the types of PK isozymes expressed in small amounts, which are very difficult to detect using the conventional PK polyacrylamide gel electrophoretic method.

Two new erythrocyte pyruvate kinase (PK) variants with severe nonspherocytic hemolytic anemia are presented. These cases are both considered to be homozygous because of the consanguineous marriages in their parents. Their erythrocyte PK's were characterized by the recommended methods of the International Committee for Standardization in Haematology (ICSH). These two variants have been named PK Sendai and PK Shinshu. PK Sendai showed a high K0.5S (phosphoenolpyruvate), was remarkably inhibited by ATP, and was thermolabile, while PK Shinshu demonstrated remarkably low enzyme activity and required a high level of fructose 1,6-diphosphate for activation.

Pyruvate kinase(PK) has four isozymes (L,R.M1,M2) that are encoded mainly by two different genes. We isolated a cDNA clone from a japanese adult liver λgt10 cDNA library by using a rat liver(L)-type PK cDNA probe. One positively hybridizing clone, hlPK-1, which contained a 1,049-base pair cDNA inset, was subjected to DNA sequence analysis. Comparisons of the sequence data with the rat PK cDNAs indicated that the cDNA encoded information for the carboxyl terminal 105 amino acids of a human L-type PK and a 3′untranslated region of 734 nucleotides. Furthermore, the karyotype analysis of several human-mouse hybrid cells and Southern blot analysis of DNAs of the hybrids with a hlPK-1 indicated that the human L-type PK gene is located on chromosome 1.