Ionic conduction mechanism in Ca-doped lanthanum oxychloride.

The mechanism of ionic conduction in Ca-doped lanthanum oxychloride (LaOCl) was investigated using first-principles calculations based on density functional theory. The calculations of the point defect formation energies suggest that Cl- ion vacancies and substituted Ca2+ ions at La sites were dominant point defects. Although the migration energy of an O2- ion is 0.95 eV, the migration energy of a Cl- ion was calculated to be 0.44 eV, which is consistent with the reported experimental value. These results imply that the main carrier in Ca-doped LaOCl is Cl- ions and ionic conduction occurs by a Cl- ion vacancy mechanism.

[Four cases of therapy-related leukemia in multiple myeloma].

We have experienced 4 cases of therapy-related leukemia (TRL) in 119 patients with multiple myeloma (MM) who had received combination chemotherapy including alkylating agents between 1988 and 1998. All 4 cases were acute myelogenous leukemia, 3 were males and 1 was female. Median age at diagnosis of MM was 60 years, and median time to TRL from diagnosis of MM was 5.5 years. The chromosome abnormalities were found in 3 of those cases. All 4 cases were resistant to antileukemic chemotherapy, and median survival time from TRL was only 5.5 months. The TRL in MM is thought to be a more important problem, because recently the treatment for this disease has become more intensive, including high-dose chemotherapy supported by autologous stem cell transplantation.

Prognostic significance of the serum phosphorus level and its relationship with other prognostic factors in multiple myeloma.

We studied the serum phosphorus (P) level of 110 patients with multiple myeloma (MM) (age range 42-83 years, median 62 years) and evaluated the relationship between that and other prognostic factors. Serum P level significantly correlated with the prognostic factors that are relevant to renal dysfunction: serum creatinine (P<0.00000001), serum beta2-microglobulin (P=0.00000088), serum uric acid (P=0.0000014), and corrected serum calcium (cCa P=0.000067). Although it also correlated with the percentage of plasma cells in bone marrow nucleated cells (BMPC%) and the hemoglobin (Hb) and leukocyte counts, the significance was less than for the other four prognostic factors. Serum creatinine, BMPC%, leukocyte count, serum uric acid, bone lesions, beta2-microglobulin, and serum cCa were all significantly higher and Hb significantly was lower in the MM patients with hyperphosphatemia (serum P>3.8 mg/dl). The survival time was significantly shorter in these patients (P=0.000087). Multivariate analysis (Cox's proportional hazards regression model) showed that the serum P level is a significant negative prognostic factor in MM patients.

[Malignant lymphoma, multiple myeloma and myeloproliferative diseases in the elderly].

Hematopoietic and immune function tend to deteriorate in the elderly. The incidence of hematologic diseases in the elderly is increasing as the percentage of elderly people in the whole population increases. Acute leukemia, myelodysplastic syndrome, malignant lymphoma, multiple myeloma, and myelodysplastic syndromes are commonly seen in the elderly. Malignant lymphomas are frequently seen in the elderly, and many elderly patients have poor performance status, and because they are more likely to suffer from impaired cardiac, respiratory, hepatic and renal function, as well as glucose intolerance, they are also more likely to suffer side effects due to chemotherapy. Particularly in patients aged over 80 years, to avoid side effects it is essential to adjust dosage and route of administration of chemotherapy. Although age is a significant negative prognostic factor for non-Hodgkin's lymphoma, it is possible for patients to enter complete remission with improvement of host-side factors. The clinical application of Rituximab is expected to improve chemotherapy outcomes in elderly B-cell lymphoma. The median age at the time of initial diagnosis of multiple myeloma (MM) is 60-70 years, and age is a negative prognostic factor. Clinically, higher rates of infection and heavy comorbidity are characteristic of this condition in the elderly. Although the incidence of bony lesions in elderly patients with MM is not different from the non-elderly, they do have a higher incidence of bone pain and pathologic fractures compared with the non-elderly patients. As the response to chemotherapy is good in the elderly, it is worth trying chemotherapy for MM. Polycythemia vera must be treated in the elderly, because chemotherapy decreases the incidence of thrombosis.

[Cytogenetic remission 10 years after the start of monotherapy with interferon alpha-2b in elderly chronic myelogenous leukemia].

A 69-year-old man was found to have leukocytosis and a bleeding tendency, when he underwent surgery for hemorrhoids in November 1992, at the age of 69. The patient was referred to our department for further examination, and was admitted on December 4. On admission, he had hepatomegaly (5 cm) and splenomegaly (12 cm). Laboratory data on admission showed that the leukocyte count was 173,400/microliter, erythrocyte count, 314 x 10(4)/microliter, hemoglobin level, 10.5 g/dl, hematocrit value, 29.7%, and platelet count, 14.4 x 10(4)/microliter, respectively. Peripheral hemogram revealed neutrophilia with a shift to the left to promyelocytes, and the positivity of neutrophil alkaline phosphatase (NAP) was very low. The bone marrow was hyperplastic with a high M/E ratio (5.8). As the chromosome analysis revealed that he had 9:22 translocation in all 20 karyotypes, chronic myelogenous leukemia in the chronic phase, was diagnosed. After the daily intramuscular administration of 9 megaunits interferon alpha-2b was started on December 9, 1992, his leukocyte count stabilized between 5,000 and 8,000/microliter. Thereafter, intramuscular administration of IFN alpha has been continued regularly almost twice a week at the outpatient clinic until now. The leukocyte count ranges from 3,000 to 6,000/ml and he is asymptomatic. In April 1995, complete cytogenetic response was achieved 28 months after the start of interferon alpha therapy. The recent bone marrow chromosomes examination showed Philadelphia-negative metaphases until now, December, 2002, although major bcr-abl still remains positive. This case suggests that treatment with interferon alpha may still be useful in some elderly patients with chronic myelogenous leukemia.

Selective enhancement of B cell antigen receptor-mediated antigen presentation by treatment with transforming growth factor-beta.

TGF-beta1 was examined for the ability to regulate Ag-presentation by B cells, using A20-HL B lymphoma cells bearing TNP-specific IgM receptors. Treatment of A20-HL cells with TGF-beta1 at 1 ng/ml, a concentration that inhibited proliferation, enhanced presentation of Ag internalized via surface IgM (sIgM), but not via fluid-phase pinocytosis. TGF-beta1-treatment slightly enhanced surface expression of sIgM, but not of MHC class II molecules. The treatment accelerated recovery of sIgM expression after its removal by ligation with TNP-OVA, and induced prolonged intracellular residence of TNP-OVA internalized via sIgM, which co-localized with intracellular MHC class II molecules. TGF-beta1-treatment increased accumulation of newly synthesized intracellular MHC class II molecules that were localized in compartments positive for lysosome-associated membrane protein 1, although cellular protein synthesis was decreased by the treatment. The accumulated intracellular MHC class II molecules were triggered to the cell surface by ligation of sIgM. Finally, TGF-beta1-treatment induced Igalpha-phosphorylation in response to lower concentrations of TNP-OVA. On the basis of these findings, we conclude that TGF-beta1-treatment of A20-HL cells selectively enhances the ability to present Ag internalized via sIgM, not via fluid-phase pinocytosis, through accelerating sIgM recovery, increasing accumulation of intracellular MHC class II molecules and enhancing the ability of sIgM ligation to induce Igalpha-phosphorylation.

[Therapeutic effectiveness of ranimustine chemotherapy for essential thrombocythemia in the elderly].

We studied the therapeutic effectiveness of chemotherapy by ranimustine (MCNU) for essential thrombocythemia (ET) in 14 ET patients over 60 years of age. The median age was 73 years (range: 61-88 years), and the male/female ratio was 6:8. The mean platelet counts before chemotherapy was 1,157 +/- 28.4 x 10(3)/microliter. Five of them had been referred because of thrombotic episodes before admission to our hospital, while one was referred because of nasal bleeding. The platelet counts were maintained at a level below 500 x 10(3)/microliter by intravenous administration of MCNU in 12 patients and below 700 x 10(3)/microliter in two patients. One of the patients suffered cerebral infarction during MCNU therapy. No other patient suffered thrombotic episodes during MCNU therapy. The patient who was referred because of nasal bleeding had no hemorrhagic episode during control of platelet counts by chemotherapy. MCNU chemotherapy appears effective for the prevention of thrombosis and bleeding in ET.

[Bone lesions in elderly multiple myeloma].

We investigated the incidence of bone lesions in elderly cases of multiple myeloma (MM) and the course of those lesions, and also evaluated the relationships of skeletal symptoms with prognostic factors, and prognosis. The subjects were 146 patients, aged 65 years or more (median age 74, range 65-97 year), who were admitted to 11 institutions between January, 1988 and December, 1997. They consisted of 64 men and 82 women. The disease type was IgG type in 88 patients, IgA type in 37 patients, Bence-Jones (BJ) type in 17 patients, IgD type in three patients, and non-secretory type in one patient. Bone lesions in elderly MM patients were compared with those in 65 non-elderly MM patients. Skeletal symptoms were noted in 104 patients, and bone pain in 75 patients at the time of diagnosis. The bone lesions were evaluated as only osteolytic lesions in 26 patients, osteolytic lesions + osteoporosis in 23 patients, only osteoporosis in 2 patients and pathologic bone fractures in 53 patients. The occurrence rate of osteoporosis plus osteolytic lesion was higher in elderly patients (63.5%) than that in non-elderly patients (NE-MM group) (28.3%) (p < 0.0001). The bone lesions were most often observed in lumbar vertebrae (58.7%), cranial bone (56.7%), thoracic vertebrae (40.4%) and ribs (27.9%). The occurrence rate of bone lesion in lumbar vertebrae was higher in elderly patients (58.7%) than that in non-elderly patients (22.6%) (p < 0.0001). The life activities were limited in 71 patients because of the bone lesions. The relationship between the prognostic factors of MM and bone lesions was evaluated. There was a significant difference in the serum Ca level between patients with and without bone pain (P < 0.0001) and between those with and without pathologic bone fracture (P < 0.01). There was a significant difference in the appearance rate of plasma cells in the bone marrow between the patients with and without bone lesions (P < 0.05), between those with and without bone pain (P < 0.01), and between those with and without pathologic fracture (P < 0.05). There was a significant difference in the serum beta 2-microglobulin level between the patients with and without bone pain, and between those with and without pathologic fracture. There were no significant differences in survival times between elderly MM patients with and without bone lesions, bone pain and pathological bone fractures, while significant differences of survival times were found between non-elderly MM patients with and without bone lesions, bone pain and pathological bone fractures (P < 0.05, each). These data suggest that there are some differences in bone lesions between elderly and non-elderly MM patients.