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Biomedical subjects

A Kanamaru

Publications and source records attributed to A Kanamaru.

At least 91 records · Page 5Linked to original sources
PubMed1998

Clonal analysis of hematopoietic cells using a novel polymorphic site of the X chromosome.

Clonality of hematopoietic cells on a smale scale (nanogram amounts of DNA) can be detected by X-chromosome inactivation using the polymerase chain reaction (PCR). The human androgen-receptor gene (HUMARA) has a polymorphic short tandem repeat (STR), and has generally been used for clonality analysis since heterozygosity for the gene occurs in 90% of caucasian females. We examined heterozygosity of the STR on HUMARA in 110 Japanese females and found heterozygosity in 74 of 110 (67%). To examine for hematologic clonality in females with HUMARA homozygosity, we used a primer specific for a novel polymorphic STR site between DXS15 and DXS134 (DXS15-134) on Xq28. Heterozygosity for this site was found in 50 of 110 females (46%). Clonality of the hematopoietic cells was detected in 91 of 110 females (83%) using PCR of either the STR sites on HUMARA or DXS15-134. The X-inactivation patterns using PCR of DXS15-134 corresponded exactly with those obtained using PCR of HUMARA in 18 females who were heterozygous for both DXS15-134 and HUMARA. Using PCR of DXS15-134, we examined the clonality of bone marrow cells separated by flow cytometry in a patient with erythroleukemia (M6). Clonality was found not only in myeloid lineage cells but also in B lymphocytes. The clonality assay for DXS15-134 may be useful to assess for clonality of hematopoietic cells in the Japanese population, when combined with the HUMARA assay.

Base Sequence↗
PubMed1998

The accuracy and clinical performance of a new compact ambulatory blood pressure monitoring device, the ES-H531.

The validity and clinical performance of the ES-H531, a newly developed ambulatory blood pressure (BP) monitoring device, were evaluated. The validity was assessed by simultaneous comparisons (total of 223 measurements) with the measurements made by two experienced observers using standard mercury column sphygmomanometers in 121 subjects. The clinical performance was evaluated through the number of measurement failures by observation of the cuff equipped site, and tolerability was assessed by administering a questionnaire to 30 of the subjects following completion of 24-h BP monitoring. The differences in systolic and in diastolic BP measured by the standard auscultation method and that measured with the ES-H531 by the Korotkoff method (K method) was 0.9+/-3.7 mm Hg (mean+/-standard deviation) and 0.1+/-3.2 mm Hg, respectively. These values satisfy the accuracy criteria of the American Association of Medical Instruments (AAMI) and accord with the grade of A in the accuracy criteria of the British Hypertension Society (BHS). The mean difference in systolic and in diastolic BP as assessed by the standard auscultation method and with the ES-H531 by the oscillometric method (O method) was 1.1+/-4.6 mm Hg and 2.7+/-5.4 mm Hg, respectively. This accords with grade B in the BHS accuracy criteria. Failures or errors in measurement occurred in 4.4% of the readings. A few subjects experienced discomfort because of noise or pain during measurements. The ES-H 531, a new compact and light weight ambulatory BP monitoring device, offers acceptable validity and sufficient comfort for clinical use.

Adult↗
PubMed1998

Recombinant human erythropoietin for late-onset anemia after allogeneic bone marrow transplantation.

Recombinant human erythropoietin (rHu EPO) has been reported to accelerate early erythroid reconstitution after bone marrow transplantation (BMT). We conducted a pilot study on rHu EPO for late-onset anemia in 9 patients after allogeneic BMT. The patients achieved initial erythropoietic recovery (hemoglobin (Hb) range 9.1-13.4, mean 10.8 g/dl), but then developed transplant-related anemia (Hb range 6.3-9.7, mean 8.2 g/dl) more than 50 days after BMT. This type of anemia was related to graft-versus-host disease (GVHD), cytomegalovirus infection, and/or impaired EPO secretion. The patients received 3,000 or 12,000 U of rHu EPO subcutaneously three or seven times weekly. Hb levels increased by more than 2 g/dl in 6 of the 9 patients, but were unchanged in the 3 patients with severe GVHD. These findings suggest that in some cases rHu EPO is effective for the treatment of late-onset anemia after BMT.

Adult↗
PubMed1998

Myelodysplastic syndrome with B cell clonality in a patient five years after renal transplantation.

A female patient received a renal transplantation from an unrelated cadaver donor, and five years later developed myelodysplastic syndrome (MDS) with immunological abnormalities. Chromosomal analysis showed trisomy 8 in bone marrow cells. FISH analysis indicated that trisomy 8 was present in 4% of CD19 + cells, suggesting that the MDS clone involved B lymphocytes. Polymerase chain reaction of the human androgen receptor gene indicated B cell clonality (54%) and granulocyte clonality (63%). There have been no previous reports of secondary MDS following renal transplantation in which the MDS clone involved the B cell lineage. The abnormal MDS B cell clone may have caused the immunological abnormalities.

B-Lymphocytes↗
PubMed1998

Response-oriented individualized induction therapy with six drugs followed by four courses of intensive consolidation, 1 year maintenance and intensification therapy: the ALL90 study of the Japan Adult Leukemia Study Group.

Adult patients with acute lymphoblastic leukemia (ALL) were treated according to the ALL90 study, the second prospective study for ALL of the Japan Adult Leukemia Study Group (JALSG). Its characteristics included response-oriented individualized induction therapy with six drugs (doxorubicin, mitoxantrone, vincristine, prednisolone, [corrected] cyclophosphamide and L-asparaginase), and a prospective comparison between allogeneic bone marrow transplantation (allo-BMT) and chemotherapy alone in patients below 45 years of age. The protocol consisted of one or two courses of induction, four courses of consolidation, and three courses of intensification including 12 month maintenance and six times of central nervous system (CNS) prophylaxis. Of 180 evaluable patients (median age, 43), 125 (69%) achieved complete remission (CR). Predicted overall survival (OAS), event-free survival and disease-free survival (DFS) were 15, 10 and 14%, respectively at the median follow-up period of 62 months. No specific toxicities were observed. Leukocytes < 30,000/microliter, normal karyotype, and blasts < 10% in bone marrow at day 15 of induction therapy were significantly favorable prognostic factors for the achievement of CR, DFS and OAS by univariate analysis. Multivariate analysis showed leukocytes < 30,000/microliter and blasts < 10% on day 15 was a significant factor for the achievement of CR, DFS and OAS. Ph-chromosome was found in 28% (36/130) of patients examined and was one of the worst prognostic factors. All Ph positive patients were predicted to die within 600 days. Allo-BMT was not significantly superior to chemotherapy with respect to DFS (P = 0.226). The overall results were inferior to those of the former ALL87 protocol. As reasons, the older median age of 43 years old (vs. 38 years old) and lower dose intensity, especially of l-asparaginase, etc. were suggested. However, patients with good prognostic factors (leukocyte < 30,000/microliter and age < 30 years old) showed better survival than others (P < 0.0001), and the result was similar to that of older children, the high risk group of childhood ALL, suggesting that ALL could be a disease of single entity, showing higher resistance to chemotherapy as patients become older.

Adult↗
PubMed1998

The levels of soluble P-selectin, von Willebrand factor and thrombomodulin in patients with neurological complications after allogeneic bone marrow transplantation.

We encountered two patients with uncommon neurological manifestations after allogeneic bone marrow transplantation (BMT), which occurred with rapid elevation of the leukocyte count at engraftment. Both patients then developed severe acute graft-versus-host disease (GVHD). To investigate the pathogenesis, we measured the levels of soluble P-selectin, von Willebrand factor (vWF) and thrombomodulin (TM), which reflect endothelial damage. The P-selectin, vWF and TM levels in the patients with (n=2) and without (n=5) neurotoxicity were, respectively, 168.5+/-52.5 ng/ml vs 27.7+/-3.9 ng/ml, 6.7+/-0.15 FU/ml vs 3.42+/-0.41 FU/ml and 459+/-37% vs 189.4+/-32.4% (mean+/-s.d.). All three parameters were much higher in the patients with neurological complications. These results suggest that neurotoxicity after BMT may be related to endothelial damage.

Adult↗
PubMed1998

Effects of chest wall vibration on breathlessness during hypercapnic ventilatory response.

Vibratory stimulation applied to the chest wall during inspiration reduces the intensity of breathlessness, whereas the same stimulation during expiration has no effect or may increase breathlessness. The purpose of the present study was to determine whether vibration reduced the intensity of breathlessness during progressive hypercapnia with and without the addition of an external resistive load. A second objective was to see whether the mouth occlusion pressure at 0.2 s (P0.2) was reduced by the vibratory stimulation. Hypercapnic ventilatory response was conducted in 10 healthy male volunteers with simultaneous measurement of visual analog scale, P0.2, and minute ventilation. Hypercapnic ventilatory response was performed and randomly combined with or without vibratory stimulation (100 Hz) as well as with or without inspiratory load. With inspiratory load, in-phase vibration did not cause any significant changes in the slopes of P0.2 and minute ventilation to CO2, whereas the slope of visual analog scale to CO2 significantly decreased from 0.47 +/- 0.15 to 0.34 +/- 0.11 (SE) cm/Torr (P < 0.05). We conclude that in-phase vibration could decrease the slope of breathlessness elicited by inspiratory load combined with hypercapnia without changing motor output.

Adult↗
PubMed1998

Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Japan Adult Leukemia Study Group.

PURPOSE: We conducted a multicenter study of differentiation therapy with all-trans retinoic acid (ATRA) followed by intensive chemotherapy in patients with newly diagnosed acute promyelocytic leukemia (APL) and analyzed the prognostic factors for predicting complete remission (CR), event-free survival (EFS), and disease-free survival (DFS). PATIENTS AND METHODS: All patients received ATRA until CR. If patients had an initial leukocyte count greater than 3.0 x 10(9)/L, they received daunorubicin (DNR) and behenoyl cytarabine (BHAC). During therapy, if patients showed blast and promyelocyte counts greater than 1.0 x 10(9)/L, they received additional DNR and BHAC. After achieving CR, patients received three courses of consolidation and six courses of maintenance/intensification chemotherapy. RESULTS: Of 198 registered, 196 were assessable (age range, 15 to 86 years; median, 46) and 173 (88%) achieved CR. Multivariate analysis showed that no or minor purpura at diagnosis (P = .0046) and age less than 30 years (P = .0076) were favorable factors for achievement of CR. Predicted 4-year overall survival and EFS rates were 74% and 54%, respectively, and the 4-year predicted DFS rate for 173 CR patients was 62%. Multivariate analysis showed that age less than 30 years (P = .0003) and initial leukocyte count less than 10 x 10(9)/L (P = .0296) were prognostic factors for longer EFS, and initial leukocyte count less than 10.0 x 10(9)/L was a sole significant prognostic factor for longer DFS (P = .0001). CONCLUSION: Our results show that age, hemorrhagic diathesis, and initial leukocyte count are prognostic factors for APL treated with ATRA followed by intensive chemotherapy.

Adolescent↗
PubMed1998

Crossroads of the effects of cyclophosphamide pulse therapy for lupus nephritis--experience of 11 cases.

In this study time for initial assessment of monthly intravenous cyclophosphamide (CP) pulse therapy is discussed for a better outcome with less complications. Eleven patients with lupus nephritis (LN) resistant to conventional therapy (serum creatinine level < or = 2.7 mg/dl) were given 500 mg/m2 of CP 7-9 times with an interval of one month. Urinary protein (Up) decreased in all patients after 3 courses of CP pulse therapy and kept similar levels thereafter. In one group of patients (n = 7), Up decreased to < 2 g/day after 3 courses, while in the other group (n = 4), it did not decrease to < 4 g/day. Creatinine clearance increased by 0-100% in the former group, while it decreased by 5-20% in the latter group after 6-9 courses. Renal function of the patients with insufficient response after 3 courses tended to show no further improvement or worsened thereafter, although Up decreased during CP pulse therapy. A relatively small dose of CP (500 mg/m2) pulse therapy was useful in most LN patients regardless of the renal histology and it was thought important to assess its effects after 3 courses for a prediction of the clinical course. Modification of the protocol at that time might be necessary in regard to dose or interval of CP administration especially for patients with insufficient outcome.

Adult↗
PubMed1998

[High-dose biweekly CHOP chemotherapy with granulocyte colony-stimulating factor support for patients with aggressive non-Hodgkin lymphoma].

A pilot study of high-dose biweekly cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) chemotherapy with granulocyte colony-stimulating factor support was carried out at 11 centers. Twenty-five patients with aggressive non-Hodgkin lymphoma under the age of 65 years old were registered. Lowest values of leukocytes and neutrophils scored grade 3 and 4 levels of Eastern Co-operative Oncology Group Toxicity Criteria in over 50% of the courses. Very rapid recovery of leukocytes and neutrophils was observed, and the duration of leukocytes under 1,000/microliter was less than 3 days in 72.2% of the courses. Leukocyte counts exceeded 2,000/microliter within 3 days in 69.1% of the courses. In most patients the hemoglobin and platelet count remained at grade 1 or 2 levels. Fever was seen in 15 out of 110 courses. In two-thirds of the 15 courses, fever disappeared within 3 days. Thus, administration of the CHOP protocol at biweekly intervals was feasible in 76.5% of the courses. Of 22 evaluable patients, there were 11 complete (CR) and 9 partial (PR) responses with an overall response rate of 90.9%. Among 13 high risk patients excluding 9 low and low-intermediate groups by International Prognostic Index, 7 CRs (53.8%) and 5 PRs (38.5%) were observed. This protocol is promising for aggressive chemotherapy of non-Hodgkin lymphoma.

Adult↗
PubMed1998

[A phase II study with high-dose cytarabine (NS-075) in adult patients with relapsed and refractory acute leukemia].

A multi-center phase II clinical study with high dose cytarabine (NS-075) was conducted in adult patients with relapsed and/or refractory acute leukemia. 2 g/m2 cytarabine was given 12 times by 3-hour intravenous infusion every 12 hrs. 46 patients were registered, and 44 were evaluable: 35 with acute myeloid leukemia (AML) and 9 with acute lymphoblastic leukemia (ALL). There were 28 males and 16 females, with a median age of 37.5 years (range 15-68), including 6 of more than 60 years. Among 35 patients with AML, there were 16 (45.7%) complete and 2 (5.7%) partial remissions. Among 9 patients with ALL, there were 2 (22.2%) complete and 1 (11.1%) partial remissions. The major non-hematologic toxicities were gastrointestinal symptoms such as nausea/vomiting, anorexia and diarrhea, as well as fever, infection, conjunctivitis, alopecia, hepatic and renal dysfunctions. Central nervous system (CNS) toxicity was mild and reversible. Therapy-related death occurred in 5 patients resulting from prolonged pancytopenia, which suggests the necessity of strict countermeasures for infections as well as good patient care. These results indicate that high-dose cytarabine is a promising therapy for treatment of relapsed and/or refractory acute leukemia.

Adolescent↗
PubMed1998

[An experience of treatment of double positive myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) and anti-glomerular basement membrane antibodies in Goodpasture's syndrome onset of crescentic glomerulonephritis].

A 68-year-old woman was admitted to Kinki University Hospital because of progressive renal failure. She had been well until two months before admission. Laboratory data were as follows: serum creatinine 4.1 mg/dl, BUN 69 mg/dl, MPO-ANCA 33 EU, anti-glomerular basement membrane antibodies (AGBMA) 118 U. Histological findings showed cellular and fibrocellular crescents in many glomeruli. Therefore, we diagnosed rapidly progressive glomerulonephritis (RPGN) due to MPO-ANCA and anti-GBM associated renal disease. The patient was started on prednisolone and double filtration plasmapheresis (DFPP) therapy. Subsequently, the values of MPO-ANCA and AGBMA decreased. However, the patient's condition suddenly worsened and she died of interstitial pneumonia. Autopsy examination revealed crescentic glomerulonephritis and alveolar hemorrhage with linear deposition of IgG along the glomerular and alveolar capillary walls by immunofluorescence studies. We considered this to be a rare case of Goodpasture's syndrome associated with not only anti-GBM antibodies, but also MPO-ANCA.

Aged↗
PubMed1997

A patient with paroxysmal nocturnal hemoglobinuria bearing four independent PIG-A mutant clones.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by clonal blood cells that are deficient in the surface expression of glycosylphosphatidylinositol-anchored proteins due to somatic mutation in the X-linked gene PIG-A. In some patients, more than one abnormal clone may be present. Analysis of bulk DNA/RNA from granulocytes has been useful in identifying the predominant PIG-A mutation in each patient. However, it is often not useful in determining the presence of minor clones. Many patients have cells with partial deficiency. Here, we analyzed the PIG-A gene in two B-cell lines bearing complete or partial deficiencies, cells of hematopoietic progenitor colonies and peripheral blood granulocytes from the same patient. We found that two B-cell lines had different mutations, the granulocytes contained at least two mutants, and the hematopoietic progenitors contained four mutants. Three of the four were shared by B cells and/or granulocytes whereas the other one was found only in the hematopoietic progenitors. The partial deficiency was caused by a point mutation near an alternative splice site within exon 2 that resulted in partial decreases of activity and quantity of the full-length transcript. These results further show the oligoclonal nature of PNH and differences in extent of expansion among mutant clones.

Alternative Splicing↗
PubMed1997

All-trans retinoic acid therapy for newly diagnosed acute promyelocytic leukemia: comparison with intensive chemotherapy. The Japan Adult Leukemia Study Group (JALSG).

We analyzed the results of treating patients with newly diagnosed acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) in the JALSG AML-92 study and compared them with those of the AML-87 and AML-89 studies, which consisted of standard chemotherapy. In the AML-92 study, patients were scheduled to receive 45 mg/ m2 oral ATRA daily until achievement of a complete remission (CR). If patients had initial leukocyte counts of > 3.0 x 10(9)/l, they received 40 mg/m2 daunorubicin (DNR) for 3 days and 200 mg/m2 behenoyl cytarabine (BHAC) for 5 days in addition to ATRA. During remission induction therapy, if the patients showed peripheral blood myeloblast and promyelocyte counts of > 1.0 x 10(9)/l, they received additional DNR and BHAC on the same schedule. After achievement of a CR, patients received three courses of consolidation and six courses of maintenance/intensification chemotherapy. Of 196 evaluable patients, 173 (88%) achieved a CR: 59 of 62 (95%) treated with ATRA alone, 41 of 49 (84%) treated with ATRA plus later chemotherapy, 63 of 73 (86%) treated with ATRA plus initial chemotherapy, and 10 of 12 (83%) treated with ATRA plus both initial and later chemotherapy. The CR rate in AML-92 was significantly higher than that in AML-89, but not than that achieved in AML-87. In addition, the early mortality and relapse rates in AML-92 were significantly lower than those in AML-89, but were not than those in AML-87. At a median follow-up of 36 months the predicted 4-year event-free survival (EFS) rate for 196 evaluable patients and the 4-year disease-free survival (DFS) rate for the CR cases were 54% and 62%, respectively. There was a significant difference in DFS between AML-92 and AML-87 (P = 0.0418) but not between AML-92 and AML-89 (P = 0.0687). In contrast, significant differences in EFS between AML-92 and both AML-87 (P = 0.0129) and AML-89 (P = 0.005) were observed. These results suggest that non-cross-resistant therapy combined with ATRA and intensive chemotherapy for APL contributes synergistically to the significant improvement in EFS.

Adolescent↗
PubMed1997

Correlation between immunological abnormalities and prognosis in myelodysplastic syndrome patients.

Immunological abnormalities (IA) are frequently observed in patients with myelodysplastic syndromes (MDS). Although there have been a number of analyses of the prognostic factors, there have been few studies, if any, to determine whether IA affects prognosis. We investigated the prognosis of 153 MDS patients with or without IA who were treated at a single Japanese institute for 10 years. Nineteen of 153 patients (12%) developed autoimmune disorders. One hundred of 153 patients (63%) had an abnormality in at least one immunological laboratory test. Hypergammaglobulinemia was found in 50 of 128 (39%) patients tested, hypogammaglobulinemia was observed in 10 of 128 (8%), positivities of antinuclear antibody, RA factor. DNA antibody, and direct antiglobulin test were observed in 30%, 14%, 7% and 12%, respectively, and a CD4/CD8 ratio < 1 was observed in 20%. There was no significance in the distribution of age, MDS subtype, or sex between patients with and without IA. The survival of MDS patients without IA was significantly better than that of patients with IA, and the survival of patients with a CD4/CD8 ratio > 1 was also significantly superior to the survival of those with an inverted CD4/CD8 ratio. Patients with IA tended to die of infection or leukemic progression in comparison with those without IA, suggesting that IA may be associated with susceptibility to opportunistic infection and disease progression.

Adult↗
PubMed1997

Second allogeneic bone marrow transplantation for post-transplant leukemia relapse: results of a survey of 66 cases in 24 Japanese institutes.

To assess the consequence of second BMT (BMT2) for leukemia relapse after allogeneic BMT, we analyzed the clinical course of 66 recipients who were treated by BMT2 in Japan. Diagnoses included 29 ANLL, 27 ALL, six CML and four MDS. Durations between the first BMT (BMT1) to relapse and BMT1 to BMT2 were 13.5 +/- 13.7 months and 17.4 +/- 13.9 months, respectively. Donors for BMT2 were replaced in 11 cases. Thirty-one patients were in CR (or CP) at BMT2. Earlier deaths were observed in those who received BMT2 within 12 months after BMT1, mostly caused by regimen-related toxicity and infections. Overall leukemia-free survival rate was 28% at 2 years and 16% at 4 years. Factors influencing the poor prognosis after BMT2 were early (<6 months) relapse, early (<12 months) BMT2, not in remission at BMT2, and ALL. Intensified conditioning did not affect either remission duration or LFS. Among the 39 cases observed for more than 100 days, 18 developed chronic GVHD (cGVHD) and showed longer remission duration than those without cGVHD. Our analysis indicates that BMT2 as treatment for leukemia relapse is effective in selected cases, and exploration of pre-BMT treatment and post-BMT immunotherapy is warranted.

Adolescent↗