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Biomedical subjects

A Kanamaru

Publications and source records attributed to A Kanamaru.

At least 127 records · Page 7Linked to original sources

Flow cytometric analysis of homologous restriction factor 20KD (HRF20) expression on progeny cells during differentiation from haemopoietic progenitors in paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder with a deficiency of glycosylphosphatidylinositol (GPI) anchored proteins. Homologous restriction factor 20KD (HRF20, CD59) is a GPI-anchored and major complement-regulatory protein which plays a key role in the haemolytic mechanism of PNH. We examined the differentiation stage at which the PNH abnormality occurs, by means of flow cytometric analysis of HRF20 expression. Non-phagocytic mononuclear marrow cells were labelled with anti-HRF20 monoclonal antibody and sorted into either HRF20-negative or -positive fractions. The sorted cells were cultured in methylcellulose and their progeny in the colonies or bursts were analysed for HRF20 expression. All colonies and bursts from HRF20-negative fractions remained negative, whereas those from HRF20-positive fractions were either positive or negative. The possibility of a sorting error was excluded, because the secondary colonies from the HRF20 positive primary colonies consisted of both positive and negative progeny. These results suggest that there are several stages during differentiation from early progenitors to mature cells, at which the PNH abnormality becomes manifest.

Blood Proteins↗

Effect of acupuncture at the Hoku point on vibration-induced finger flexion reflex in man: comparison between press needle technique, electroacupuncture, and in-situ technique.

Effects of press needle technique (PN), electroacupuncture (EA), or in-situ technique (IS) on vibration-induced finger flexion reflex (VFR) were examined in 31 healthy adults. VFR, which is tonic finger flexion evoked by vibration applied to the finger tip, was induced by vibrating the volar side of the middle finger tip before and after acupuncture. Acupuncture was applied to the Hoku point on both sides. The three techniques, each studied on separate days, inhibited VFR and there was no significant difference in VFR inhibition among the three techniques (percentage of pre-acupuncture VFR was 71.5 +/- SE 2.2% after PN, 72.6 +/- SE 2.4% after EA, and 75.6 +/- SE 2.8% after IS). The results suggest that afferent signals from muscles contracting due to electrical stimulation had no significant effect on the reflex arcs of VFR; and that the intradermal stimulation by acupuncture played a significant role in VFR inhibition.

Acupuncture Therapy↗

De-novo acute myeloid leukemia with trilineage myelodysplasia (AML/TMDS) and myelodysplastic remission marrow (AML/MRM).

Trilineage myelodysplasia (TMDS) in de novo acute myeloid leukemia (AML) at initial diagnosis and during remission has not been well recognized yet. In this review we describe the characteristics of de novo AML with TMDS (AML/TMDS) and with myelodysplastic remission marrow (AML/MRM) in view of the in vivo and in vitro disease progression. AML/TMDS was found in ten (10.4%) of 96 patients with de novo AML at initial diagnosis and AML/MRM were also observed in three (5.0%) out of 60 cases in remission after chemotherapy in our hospital between 1984 and 1992. Abnormal karyotypes were seen in six of nine AML/TMDS patients and all of the three AML/MRM. Karyotypic changes occurred in two of AML/TMDS and two of AML/MRM during their clinical course. Using the long term bone marrow culture (LTBMC) system that allowed abnormal clones to survive preferentially to the clone of normal karyotype, latent clones were detected in three patients with AML/TMDS and three of AML/MRM as in the cases of myelodysplastic syndrome (MDS) and AML transformed from MDS (MDS/AML) but not in the typical AML without myelodysplastic changes. Four of these cases exhibited the same karyotypes as seen during the clinical course. Primary abnormal karyotypes prior to clonal evolution were also observed in two of the AML/MRM. Taken together, both AML/TMDS and AML/MRM are similar to MDS/AML with respect to their myelodysplastic background and potential for disease progression and may have progressed to AML from the preceding disease status more rapidly than MDS/AML.

Acute Disease↗

FK506 treatment of graft-versus-host disease developing or exacerbating during prophylaxis and therapy with cyclosporin and/or other immunosuppressants. Japanese FK506 BMT Study Group.

A phase II study of the efficacy and safety of FK506, a new potent immunosuppressant, has been conducted in 49 patients with GVHD after allogeneic BMT. Eighteen patients with acute GVHD and 31 with chronic GVHD entered the study. FK506 was administered at an initial dose of 0.05 mg/kg i.v. or 0.15 mg/kg orally twice a day to those whose GVHD had become uncontrollable with cyclosporin and/or other immunosuppressants. The response to FK506 was evaluated in 13 patients with acute and 26 with chronic GVHD. A marked response was observed in 5 and a good response in 2 of 13 patients with acute GVHD. For those with chronic GVHD, the response was marked in 2 patients, good in 10 and poor in 8. The most common adverse effects were renal toxicity (53.1%), followed by nausea and vomiting (30.6%) and a feeding of warmth (18.4%). There was a correlation between renal toxicity and whole blood levels of FK506. The dose should be adjusted to keep a trough level between 15 and 25 ng/ml. FK506 is promising in the treatment of both acute and chronic GVHD, even if it is intractable with other immunosuppressants, and may be most effective if administered early in the course of GVHD.

Acute Disease↗

A double-blind controlled study of granulocyte colony-stimulating factor started two days before induction chemotherapy in refractory acute myeloid leukemia. Kohseisho Leukemia Study Group.

We conducted a prospective, double-blind controlled study to determine the efficacy of a recombinant granulocyte colony-stimulating factor (G-CSF, 200 microgram/m2) starting daily from 2 days before an induction therapy until neutrophils recovered to above 1,500/microL or until 35 days after the therapy in 58 patients with relapsed or refractory acute myeloid leukemia (AML). Twenty-eight patients in the G-CSF group showed significantly faster recovery of neutrophils (P < .001) than 30 patients in the placebo group. The incidence of febrile episodes and of documented infections was almost the same in both groups. However, among 39 patients who did not show any infectious episodes during the 2-week period after the start of chemotherapy, the incidence of documented infections after the third week tended to be lower in the G-CSF group, but not statistically significantly. There was no evidence that G-CSF stimulated the growth of AML cells in the bone marrow during the 2-day period before the chemotherapy, nor that G-CSF accelerated the regrowth of AML cells during the 5-week period after the therapy. Fifty percent of patients in the G-CSF group and 37% in the placebo group had complete remission (CR). Although the rate was higher in the G-CSF group, the difference was not statistically significant (P = .306). There was no difference between the two groups in event-free survival of all patients and in disease-free survival of patients who had achieved CR.

Adolescent↗

Effect of chest wall vibration on dyspnea in patients with chronic respiratory disease.

The effect of chest wall vibration on dyspnea at rest was investigated in 15 patients with severe chronic respiratory diseases. The magnitude of their baseline dyspnea was 17.9 +/- SE 3.3 mm on a 150-mm visual analog scale. One hundred hertz out-of-phase vibration (OPV; inspiratory intercostal muscles vibrated during expiration and expiratory intercostal muscles vibrated during inspiration) increased dyspnea an average of 21.9 +/- SE 7.8 mm (p < 0.05). One hundred hertz in-phase vibration (IPV; inspiratory intercostal muscles vibrated during inspiration and expiratory intercostal muscles vibrated during expiration) decreased dyspnea an average of 6.9 +/- SE 2.8 mm (p < 0.05). Changes in the respiratory pattern and arterial blood gas determinations elicited by 5-min IPV were investigated in eight of the 15 patients. Tidal volume was significantly increased in all eight of these patients. Respiratory frequency was decreased in seven patients and increased in one. Functional residual capacity, measured before and during the application of IPV for a period of about 10 breaths, was increased in one patient and decreased in the remaining seven. PaCO2 decreased by 1.3 +/- 1.0 mm Hg (p < 0.05), from 49.6 +/- 8.4 mm Hg; PaO2 increased by 3.4 +/- 2.3 mm Hg (p < 0.05), from 67.7 +/- 12.7 mm Hg. The results indicate that in-phase chest wall vibration decreased pathologic dyspnea in patients with chronic respiratory disease and suggest that the effects on respiratory sensation are mediated by afferent information from chest wall respiratory muscles to supraspinal centers.

Aged↗

A case-control study on risk factors for leukemia in a district of Japan.

A case control study was performed with 142 leukemia patients and 284 controls matched for age and sex. Occupation, birth order, past medical history, and drinking and smoking habits were compared in these two groups. Persons born first or fourth were found to have a higher incidence of leukemia. History of a fracture was one of the risk factors for acute leukemia, and a history of gastroduodenal ulcer was a risk factor for chronic leukemia. This may suggest that extensive exposure to X-rays in diagnosis and treatment is a risk factor for leukemia. There was a significant dose-response relationship between the amount of smoking and the incidence of acute nonlymphocytic leukemia, but not between the amount of alcohol consumption and the incidence of leukemia. Thus, smoking was one of the risk factors for acute leukemia.

Aged↗

All-trans retinoic acid therapy in relapsed/refractory or newly diagnosed acute promyelocytic leukemia (APL) in Japan.

We have conducted four prospective multicenter studies for acute promyelocytic leukemia (APL) using oral 45 mg/m2 all-trans retinoic acid (ATRA) daily. The first three studies were for relapsed/refractory APL, and the fourth study for newly diagnosed APL. In the first study with ATRA alone, 18 (82%) of 22 evaluable patients achieved complete remission (CR). Initial peripheral leukemia cell counts were significantly less in the CR cases (p < 0.01); < 100/microliters in 17 of 18 CR cases, and > or = 200/microliters in all failure cases. In the second study, if initial leukemia cell counts were more than 200/microliters, chemotherapy with daunorubicin and behenoyl cytarabine was first given, and then ATRA was started. Of 42 evaluable patients, 36 (86%) achieved CR. In the third study, if initial leukemia cell counts were more than 200/microliters, chemotherapy was concomitantly given with ATRA, and if during the ATRA therapy leukemia cell counts became more than 1000/microliters, chemotherapy was added. Of 46 evaluable patients, 36 (78%) achieved CR. Patients achieving CR received standard consolidation and maintenance chemotherapy, and the 29-month predicted disease-free survival (DFS) rate is 72% for 41 cases achieving their first CR with ATRA, and 20% for 49 cases achieving their second CR with ATRA. In the fourth study for newly diagnosed APL, if leukocyte counts were more than 3000/microliters, chemotherapy was concomitantly given with ATRA, and if during the ATRA therapy leukemia cell counts became more than 1000/microliters, chemotherapy was added. Of 109 evaluable patients, 97 (89%) achieved CR, and the 19-month predicted event-free survival rate for all patients is 78%, and the DFS rate is 88% for 97 cases achieving CR. ATRA produces a high CR rate in both relapsed/refractory and newly diagnosed APL, and should be incorporated in the first-line therapy of this disease.

Adolescent↗

Generation of self HLA-DR-specific CD3+CD4-CD8+ cytotoxic T cells in chronic graft-versus-host disease.

To analyze the mechanism of chronic graft-versus-host disease (GVHD) characteristic of autoimmune disease, we used a cell-mediated lympholysis assay to study the autoreactivity of PBL from two patients after MHC-matched BMT. Our data indicate the induction of CD3+CD4-CD8+ autoreactive cytotoxic T lymphocytes (CTL) in the one patient with chronic GVHD and an important role for allo-non-MHC (minor histocompatibility) antigen-specific CD3+CD4+CD8- helper T cells in this induction. Experiments using HLA-DR gene-transfected mouse L cells as target cells and blocking assays with anti-HLA class I and class II antibodies provided evidence that autoreactive CTL recognized HLA-DR antigen on autologous cells. Analysis of antigen-specific T cell proliferative responses in these patients to examine the effect of self HLA-DR-specific CTL on the antigen presenting cell (APC)-T cell interaction suggested that donor bone marrow-derived self HLA-DR-specific CTL are responsible for the decreased antigen-presenting ability of the patient's APC. These results suggest a new interpretation of the induction mechanism of chronic GVHD and its associated immunosuppression after MHC-matched BMT based on diminished APC function.

Antibodies, Monoclonal↗

[Expression of GPI-anchor proteins during the differentiation from hematopoietic progenitors in patients with paroxysmal nocturnal hemoglobinuria].

We studied the expression of HRF20, one of the GPI-anchor proteins, on the hematopoietic progenitors and their progeny cells grown in cultures with bone marrow cells from patients with paroxysmal nocturnal hemoglobinuria (PNH). PNH bone marrow cells were sorted by fluorescence-activated cell sorter with anti-HRF20 monoclonal antibody and then cultured in methylcellulose. Every CFU-GM colonies and BFU-E bursts formed from the HRF20-negative fraction were HRF20-negative. On the other hand, there were HRF20-positive colonies and bursts as well as HRF20-negative ones in cultures with bone marrow cells from the HRF20-positive fraction. The results suggested that abnormal events can occur during the several steps of differentiation form PNH hematopoietic stem cells.

Bone Marrow Cells↗

[Clinical usefulness of visual analog scale for assessment of dyspnea at rest in patients with chronic respiratory diseases].

To evaluate the validity and clinical usefulness of the visual analog scale (VAS) for the measurement of dyspnea at rest, we employed the 150 mm VAS in 29 chronic respiratory disease patients who were clinically stable, and repeated the measurement 4 weeks and 8 weeks later for the evaluation of reproducibility. For the 8-week period, the individual medical treatments remained generally unchanged in all patients. Two patients were excluded from the study due to infection and pneumothorax. Dyspnea at rest was detected on VAS in 23 patients at the first measurement. The VAS measurement was 23.9 +/- 28.4 (mean +/- SD) mm at the first time, 22.0 +/- 23.1 mm at the 4th week, and 22.4 +/- 26.0 mm at the 8th week. There was no significant change among the three measurements. Twenty among the 23 patients with VAS indicative of dyspnea at rest were categorized into grades 4 and 5 of the Fletcher dyspnea category. However, the intensity of dyspnea was distributed widely within each Fletcher category. These results lead to the conclusion that VAS shows good reproducibility over a period of as long as 8 weeks and that VAS measurements can reveal patient-to-patient individual differences in dyspnea intensity which cannot be detected by the Fletcher dyspnea category. We propose that measuring dyspnea at rest using VAS is a useful method to obtain a valid clinical parameter.

Adult↗

Sensory reinnervation of muscle receptor in human.

This report describes sensory reinnervation of muscle receptors in humans. In this study, sensory function was investigated in fourteen patients with brachial plexus injury, whose musculocutaneous nerve was surgically sutured with intercostal nerves for reconstruction of elbow flexion. Tapping the intercostal nerve-reinnervated brachial biceps muscle (IC-biceps) induced somatosensory evoked potentials (IC-biceps SEP) in four patients. Tapping also induced reflex IC-biceps activity in all IC-biceps SEP (+) patients, but not in eight out of nine IC-biceps SEP (-) patients. Results show that muscle afferent fibers in the intercostal nerves reinnervated mechanoreceptors in IC-biceps, and induced both cortical sensory activity and muscle activity that indicated the classical stretch reflex.

Adolescent↗

Malignant lymphoma of bladder. Report of three cases and review of the literature.

BACKGROUND: The significance of long-standing cystitis has been postulated as a causal factor in malignant lymphoma of bladder. METHODS: The authors reviewed 3 cases of primary malignant lymphoma of the urinary bladder and an additional 27 cases described in the literature (25 from Western countries and 2 from Japan). Clinical and pathologic findings in the total 30 cases are summarized. RESULTS: The majority of patients presented with gross hematuria and were between 20 and 85 years of age (median age, 64 years). Marked female preponderance was found (male to female ratio, 1:6.5). Six patients (20%), all of whom were women, out of 30 had a history of chronic cystitis. Macroscopic findings showed a solitary mass (22 cases), multiple masses (6 cases), or a diffuse lesion without nodule formation (2 cases). The vast majority of bladder lymphoma were non-Hodgkin lymphoma (NHL) of B-cell type; among them, 14% were follicular lymphomas. Follow-up indicated that NHL of bladder had a favorable prognosis. CONCLUSIONS: Malignant lymphoma of bladder is characterized by a preponderance in women, who are occasionally affected by chronic cystitis.

Adult↗

Multilineage response in aplastic anemia patients following long-term administration of filgrastim (recombinant human granulocyte colony stimulating factor).

The present multicenter study was undertaken to confirm whether filgrastim/recombinant human granulocyte colony stimulating factor (rhG-CSF) could mobilize residual multipotential stem cells by its G0-shortening effect in patients with aplastic anemia (AA) and induce a multilineage response. Twenty-seven patients with acquired severe or moderate AA received long-term administration (2 to 12+ months) of rhG-CSF in doses from 100 to 400 micrograms/body/day by s.c. injection or 250 to 1,500 micrograms/body/day by i.v. infusion. Twenty-six out of the 27 evaluable patients showed a substantial increase in neutrophils associated with a recovery of myeloid precursors in bone marrow within one month of therapy. Interestingly, 10 out of the 27 patients showed a dramatic improvement in severe anemia after two to ten months of therapy. Moreover, severe thrombocytopenia improved after two to four months of therapy in three out of these ten patients accompanied by a significant increase in megakaryocytes in bone marrow. Clonal cultures of bone marrow cells revealed a recovery in myeloid as well as erythroid precursors in most of these ten patients. In two patients who showed a trilineage response, mixed and megakaryocyte colony formations also recovered. These results suggest that long-term administration of rhG-CSF mobilizes myeloid, erythroid, megakaryocyte and multipotential progenitor cells and induces a multilineage response in some patients with AA.

Adolescent↗

Implication of membrane factors other than DAF and CD59 in complement-mediated lysis of paroxysmal nocturnal hemoglobinuria erythrocytes.

Erythrocytes from two patients (F.K. and A.M.) with paroxysmal nocturnal hemoglobinuria, which were almost completely deficient in decay-accelerating factor and CD59, were found to differ in their susceptibility to homologous complement. Whereas 50-70% of F.K. erythrocytes were lysed, almost 100% of the erythrocytes from A.M. were lysed. These observations were seen under both acidified and nonacidified conditions, and regardless of whether or not the normal human serum was adsorbed with normal erythrocytes to remove natural antibodies. Erythrocytes from two other patients, J.S. and Y.K., about 85% of which did not express CD59, showed lytic profiles similar to those of patient F.K. The differences between patients were not related to levels of natural antibody or other membrane regulatory proteins such as complement receptor type I or membrane cofactor protein. Erythrocytes from F.K. and A.M. differed in their reconstitution with decay accelerating factor and CD59. While erythrocytes from F.K. were reconstituted with CD59 in a unimodal pattern, erythrocytes from A.M. showed a bimodal pattern of reconstitution assessed by flow cytometry. After reconstitution with CD59, erythrocytes from F.K. and A.M. differed in their protection against homologous complement. It is concluded that erythrocyte membrane constituents other than the known inhibitors differ in these patients.

Antigens, CD↗

Clonal evolutions during long-term cultures of bone marrow from de novo acute myeloid leukaemia with trilineage myelodysplasia and with myelodysplastic remission marrow.

We previously established a long-term bone marrow culture (LTBMC) system in which novel abnormal karyotypes could emerge in vitro prior to the appearance of the same karyotypes in vivo in patients with myelodysplastic syndrome (MDS). We extended our study to examine whether acute myeloid leukaemia (AML) transformed from MDS (MDS/AML) and de novo AML with trilineage myelodysplasia (AML/TMDS) show clonal evolution in LTBMC similar to that of typical AML or MDS. We also analysed the cytogenetic changes in cultures with bone marrows from AML with myelodysplastic remission marrow (AML/MRM) as well as chronic myeloid leukaemia (CML) to compare them with typical AML with respect to the liability of clonal evolution. Among the 34 AML cases, abnormal karyotypes were newly detected in four of seven MDS/AML, three of six AML/TMDS and three of three AML/MRM. Novel abnormal karyotypes were also observed in nine out of 13 CML cases after culture. In contrast, no other abnormal karyotypes were found after culture in 18 typical AML without myelodysplasia. These findings suggest that AML/TMDS and AML/MRM are different from typical AML and are similar to MDS/AML and CML in view of their potential for disease progression from latent multiple clones. Typical AML may develop from a single abnormal clone without any subclones.

Anemia, Aplastic↗

Effect of acupuncture at the right Hoku point on bilateral vibration-induced finger flexion reflex in man: comparison between in-situ and Sparrow Pecking technique.

The purpose of this study was to compare the effect of the Sparrow Pecking (SP) technique with that of the In-Situ (IS) technique of acupuncture on vibration-induced finger flexion reflex (VFR). Subjects were 30 healthy adults. VFR, flexion movement of the vibrated finger, was induced by vibrating the volar side of the middle finger tip. The acupuncture point was the right Hoku point. Both techniques of acupuncture inhibited VFR in the ipsilateral and contralateral sides, but inhibition with SP was significantly greater than that with IS (percentage control force of VFR, mean +/- SD: with SP right, 62.1 +/- 24.6%, left, 60.6 +/- 27.9%, with IS right, 74.9 +/- 26.6%, left, 78.1 +/- 29.5%, P < 0.0005). The results suggest that SP suppresses facilitation of VFR in the reflex arcs more than IS does.

Acupuncture Points↗

Inspiratory prolongation by vagal afferents from pulmonary mechanoreceptors in rabbits.

Graded inflation and deflation pressures were transiently applied to the airway, and the effects on the inspiratory (TI) and expiratory (TE) durations were studied in twelve Japanese white rabbits tracheotomized and anesthetized with urethane and chloralose. Without vagal cooling, lung inflation prolonged TE, whereas changes in TI were small and inconsistent. The bilateral vagus nerves were cooled to 7 degrees C to block myelinated fibers, and to study the effects of C-fiber afferents. During vagal cooling to 7 degrees C, inflation dose dependently prolonged the first TI with no consistent change in TE. Without vagal cooling, lung deflation shortened TE of the first and succeeding breaths, and prolonged TI of the first breath to manifest apneusis. Deflation applied at the vagal temperature of 7 degrees C induced slight shortening of TI and TE in 6 of the 12 rabbits. All these changes were blocked when the vagus nerves were cooled to 1 degree C. The results may indicate that vagal afferents from irritant receptors shorten TE, and C-fiber afferents prolong TI. High irritant afferent activity may markedly shorten TE, causing tidal inspiratory activities to merge and manifest apneusis. Capsaicin, which is suggested to be a "selective" stimulant of C-fiber receptors was injected into the right atrium in 4 of the 12 rabbits. The chief changes were TE shortening without vagal cooling, and TI prolongation during cooling to 7 degrees C. This suggests that capsaicin injected into the pulmonary circulation stimulates both the irritant and C-fiber receptors and the C-fiber afferents may prolong TI even when stimulated chemically.

Afferent Pathways↗