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Biomedical subjects

A Kanamaru

Publications and source records attributed to A Kanamaru.

At least 73 records · Page 4Linked to original sources

Movement related cortical source for elbow flexion in patients with branchial plexus injury after intercostal-musculocutaneous nerve crossing.

Nine patients with brachial plexus injury whose transected musculo-cutaneous nerves had been sutured with intercostal nerves were examined and the relationship between flexion of the operated elbow and the respiratory movement were shown. Three out of nine patients showed independent control of movement from respiration after regeneration. The primary motor cortex for either flexion of the elbow to the operated side or brisk voluntary inspiration was estimated in the medial vertex region of the frontal cortex by the dipole-tracing method in these three patients. The present results suggest that patients contract the biceps muscle reinnervated by the intercostal nerve independently from respiratory movements using the same primary motor cortex with trunk movements. Functional plasticity may occur in the patients using the primary trunk motor cortex for elbow flexion.

Adolescent↗

Increased interleukin-4 production by NK T cells in systemic lupus erythematosus.

It has been reported that production of interleukin (IL)-4, a T helper (Th)-2-type cytokine, might play an important role in the pathogenesis of systemic lupus erythematosus (SLE). On the other hand, it is known that NK1.1(+) cells which belong to CD4, CD8 double-negative, or CD4(+) cells are associated with initial IL-4 production and Th2 differentiation in mice although human equivalent cells are unknown. In order to study the profile of IL-4-producing cells in SLE, cytoplasmic IL-4 and various surface antigens on peripheral mononuclear cells were analyzed. Peripheral mononuclear cells were stimulated for 5 h by phorbol ester and ionomycin in the presence of monensin, fixed, and permeabilized with paraformaldehyde and saponin solution. Then cytoplasmic IL-4 and various surface antigens were analyzed by flow cytometry. IL-4-producing cells in SLE were phenotypically the same as those which produce IL-4 normally and frequently bore activated T-cell (CD7, CD25, CD28, CD29) and NK-cell markers (CD56, CD57). Double-negative T cells and CD57(+) T cells were increased in number and were more frequently positive for cytoplasmic IL-4 in SLE compared with normal controls and various infectious diseases. It was suggested that T cells with NK cell markers, CD57(+) T cells, which are known to extrathymically differentiate, might be involved in the pathogenesis of SLE as a counterpart of mouse NK1.1(+) cells.

Adult↗

Chromosomal imbalances in adult T-cell leukemia revealed by comparative genomic hybridization: gains at 14q32 and 2p16-22 in cell lines.

Comparative genomic hybridization was used to identify chromosomal imbalances in eight cell lines and 12 blood samples from patients with adult T-cell leukemia/lymphoma (ATL). The chromosomes most often over-represented in the cell lines were 2p (6 cases), 7q (4 cases), and 14q (4 cases), with minimal common regions at 2p16-22, 7q21-36, and 14q32, respectively. Distinct imbalances were detected in only 7 of the clinical samples. Chromosomes 14q32 and 2p16-22 harbor TCL1 and a transcription factor, HTLF (human T-cell leukemia virus enhancer factor), respectively. FISH analysis revealed that TCL1 did not juxtapose to TCRA, and we detected no expression of TCL1 in any of the ATL cell lines despite the 14q32 amplifications. Moreover, expression of HTLF was not elevated in the ATL cell lines bearing multiplication of 2p. These results suggest that chromosomal regions 2p16-22 and 14q32 harbor genes other than HTLF and TCL1 that are involved in cellular immortalization or in the pathogenesis of ATL.

Chromosome Aberrations↗

Thrombotic microangiopathy following allogeneic bone marrow transplantation.

Thrombotic microangiopathy is one of the complications of bone marrow transplantation and is related to other complications such as graft-versus-host disease, veno-occlusive disease, diffuse alveolar hemorrhage, and cytomegalovirus infection. Thrombotic microangiopathy occurred in three out of 12 patients who underwent allogeneic bone marrow transplantation over the past 1 year at our department. We compared the changes in cytokines and other molecules between patients with and without microangiopathy from before conditioning to the early post-transplantation period. All three patients with microangiopathy showed a significant increase of interleukin-12 at the time of leukocyte recovery after transplantation (two-way layout analysis of variance; P < 0.05), while none of the patients without microangiopathy showed an increase of interleukin-12. No significant differences were found between the two groups with respect to the other cytokines and molecules that were tested. These findings suggested that thrombotic microangiopathy might be predicted at an early stage after bone marrow transplantation by detecting an increase of interleukin-12 at the time of leukocyte recovery. The possibility that thrombotic microangiopathy is related to inflammation or autoimmunity was also suggested.

Adolescent↗

Predicting the severity of graft-versus-host disease from interleukin-10 levels after bone marrow transplantation.

Acute graft-versus-host disease (GVHD) is the most important complication of allogeneic bone marrow transplantation. We investigated the possibility of predicting severe acute GVHD using plasma interleukin-10 levels in 31 patients who underwent allogeneic bone marrow transplantation. In patients with acute GVHD, the interleukin-10 (IL-10) level increased significantly from the aplastic phase through the leukocyte recovery phase after transplantation (P < 0.05, paired t-test). The ratio of the IL-10 level in the aplastic phase to that in the leukocyte recovery phase was significantly correlated with the severity of acute GVHD (P < 0. 05, t-test), and the incidence of grade III or IV disease was significantly increased (P < 0.0001). Since IL-10 antagonizes various other cytokines that induce acute GVHD, determination of the IL-10 level is equivalent to assessing the total production of cytokines promoting GVHD. The ratio of the IL-10 level in the aplastic phase to that in the recovery phase seems to be useful for predicting the subsequent risk of acute GVHD.

Acute Disease↗

Effects of permanent tracheostomy on respiratory reflexes to lung inflation and capsaicin in sevoflurane-anaesthetized dogs.

The aim of this study was to evaluate the effects of permanent tracheostomy on baseline breathing, reflex responses to lung hyperinflation (1.5 kPa) and right atrial capsaicin injection (5 micrograms/kg) before and at 3 and 5 weeks after tracheostomy in sevoflurane-anaesthetized spontaneously breathing dogs (n = 6). In all observation periods, apnoeic responses, represented by an increase in expiration time after lung inflation and right atrial capsaicin injection, were consistently observed to be a result of the Hering-Breuer inflation reflex and the pulmonary C-fibre chemoreflex. Investigation at 3 and 5 weeks after tracheostomy revealed no significant evidence of changing baseline breathing pattern or reflex responses to lung inflation and capsaicin in any ventilatory variable (inspiration time, expiration time, tidal volume, expired ventilation, and end-tidal PCO2) from levels recorded before surgery. These results indicate that permanent tracheostomy, at least up to 5 weeks, does not affect the baseline breathing pattern, the Hering-Breuer inflation reflex or the pulmonary C-fibre chemoreflex. Further, our investigation provides a useful canine model in respiratory physiology.

Anesthetics, Inhalation↗

Redox control of Epstein-Barr virus replication by human thioredoxin/ATL-derived factor: differential regulation of lytic and latent infection.

Human thioredoxin (hTRX)/adult T-cell leukemia (ATL)-derived factor (ADF) was originally reported as an interleukin-2 (IL-2) receptor-alpha-inducing factor produced by human T-cell lymphotropic virus-1-positive (HTLV-1+) cell lines. Growing evidence indicates that hTRX/ADF plays important roles in cellular responses against oxidative stress and is involved in a variety of cellular functions. A high level of hTRX/ADF expression is also observed in other human virus-infected cell lines including those of Epstein-Barr virus (EBV) and human papillomavirus. In this report, we analyzed the effect of hTRX/ADF on lytic amplification and persistent replication of EBV as a model for lytic versus latent phase of viral replication in host cells. Addition of hTRX/ADF clearly suppressed lytic replication of EBV in Raji cells and B95-8 cells induced to the lytic phase of 12-O-tetradecanoylphorbol-13-acetate (TPA), and it prevented the death of these cells evoked by the lytic induction. In contrast, hTRX/ADF did not have any effect on persistent replication in the latent phase. These data indicated that hTRX/ADF prevents EBV-transformed cells from proceeding into the lytic phase and regulates cohabitation of EBV and its host cells.

Carcinogens↗

IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases.

Using the suppression subtractive hybridization technique, we isolated a novel kinase, IKK-i, whose message is drastically induced by lipopolysaccharide (LPS) in the mouse macrophage cell line RAW264. 7. The predicted protein contains the kinase domain in its N-terminus, which shares 30% identity to that of IKK-alpha or IKK-beta. The C-terminal portion contains a leucine zipper and a potential helix-loop-helix domain, as in the case of IKK-alpha and IKK-beta. IKK-i is expressed mainly in immune cells, and is induced in response to proinflammatory cytokines such as tumor necrosis factor-alpha, IL-1 and IL-6, in addition to LPS. Overexpression of wild-type IKK-i phosphorylated serine residues Ser32 and Ser36 of IkappaB-alpha (preferentially Ser36), and significantly stimulated NF-kappaB activation. These results suggest that IKK-i is an inducible IkappaB kinase which may play a special role in the immune response.

Amino Acid Sequence↗

Effects of volatile anesthetics on the activity of laryngeal 'drive' receptors in anesthetized dogs.

Effects of halothane, isoflurane and sevoflurane on laryngeal drive receptor activity were studied in the afferent activity of the superior laryngeal nerve in anesthetized spontaneously breathing dogs. Of 40 single units recorded, most of them (65%) responded to the volatile anesthetics applied to the isolated larynx at a concentration of 5%. The exposure to the anesthetics resulted in either an inspiratory increase (15%), both inspiratory and expiratory decrease (54%), or both inspiratory increase and expiratory decrease (31%) responses. The average discharge frequency of the receptors tended to be decreased on inhalation of the anesthetics, where significant decreases were observed in both respiratory phases for halothane and at expiration for isoflurane, but in neither respiratory phase for sevoflurane. These results support an advantage of sevoflurane over halothane and isoflurane for induction of anesthesia to minimize the influence of the activity of laryngeal drive receptors on the breathing pattern and airway stability.

Anesthetics, Inhalation↗

The posterior nasal nerve plays an important role on cardiopulmonary reflexes to nasal application of capsaicin, distilled water and l-menthol in anesthetized dogs.

The sensory innervation of the cardiopulmonary reflexes to nasal application of capsaicin (CAPS), distilled water (DW) and l-menthol (LM) was studied in anesthetized dogs breathing through tracheostomy. A marked cardiopulmonary reflex was observed by CAPS and DW into the nasal cavity, while a prolongation of expiration was induced by LM. All these reflexes were significantly decreased by bilateral section of the posterior nasal nerve (PNN) and completely abolished by topical nasal anesthesia with lidocaine. Responses of the whole nerve activity of the PNN to these substances corresponded to the magnitude of the reflexes. These results indicate that PNN afferents play an important role on the reflex elicitation of the noxious, water and cold stimuli from the nasal cavity.

Administration, Intranasal↗

Nasal sensory receptors responding to capsaicin, water and tactile stimuli in sevoflurane-anesthetized dogs.

Responses of nasal receptors to capsaicin and water were studied from afferent recordings of the posterior nasal nerve (PNN) in 12 anesthetized dogs. Out of 12 non-respiration-modulated nasal receptors, 7 responded only to capsaicin, 3 responded to both water and capsaicin, and 2 to neither of them. All the fibers showed a rapid adaptation to mechanical probing of the nasal mucosa. These results indicate that the presence of sensory receptors responding to capsaicin and water are involved in PNN afferents of the dog.

Anesthesia, Inhalation↗

Detection of GPI-anchored protein-deficient cells in patients with aplastic anaemia and evidence for clonal expansion during the clinical course.

The incidence of patients with aplastic anaemia (AA) who show a deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins on their peripheral blood (PB) or bone marrow (BM) cells is higher than that previously reported. We analysed the expression of CD55 or CD59 on PB and BM cells and those of colonies and bursts formed in cultures with marrow cells from AA patients. 4/21 (19%) AA cases later developed paroxysmal nocturnal haemoglobinuria (PNH). 7/17 (41. 2%) AA cases showed a subpopulation without GPI-anchored proteins. The defect characteristic for PNH was observed only on the colonies/bursts but not on the PB or BM cells in three cases. We found the affected colonies/bursts in cultures using thawed marrow cells which had been cryopreserved at the diagnosis of aplasia in one patient who developed PNH 3 years later. Two different mutations of the PIG-A gene were found in the colonies/bursts at the time of AA. The nucleotide sequences were identical between the colonies/bursts at the time of AA and those after the transition to PNH. However, one of the mutations was detected only at the haemopoietic progenitor level but not in PB granulocytes. There may be latent subclones with PNH abnormalities which could expand to the level of clinical detection, or which do not progress and remain indolent for a relatively long time, implying the different extents of clonal expansion among the affected progenitors.

Adolescent↗

Fluconazole versus amphotericin B for the prevention of fungal infection in neutropenic patients with hematologic malignancy.

Effective prophylaxis against fungal infection is important in neutropenic patients with hematologic malignancies, but the best method remains unclear. We investigated the effectiveness of fungal prophylaxis with amphotericin B or fluconazole. We reviewed the data on fungal isolates, plasma (1-->3)-beta-D glucan (beta-D glucan) levels, febrile periods (the number of days with an axillary temperature > 38 degrees C), and the duration of an axillary temperature > 38 degrees C when the neutrophil count was < 500/microliter. Of the 124 patients studied, 57 had acute myelogenous leukemia, 19 had acute lymphoblastic leukemia, 18 had non-Hodgkin's lymphoma, six had chronic myeloid leukemia, three had adult T-cell leukemia, and five had chronic lymphocytic leukemia. There were no significant differences in clinical characteristics between the 70 patients treated with amphotericin B and the 54 patients given fluconazole. There was a significant decrease of fungal isolates (chi 2-test, p < 0.001), the plasma beta-D glucan level (Wilcoxon test, p = 0.0001), and the febrile period (t-test, p < 0.05) in the patients given fluconazole compared with those given amphotericin B. In neutropenic patients with hematologic malignancies, prophylaxis with fluconazole significantly decreased fungal isolation and other indicators of fungal infection when compared with amphotericin B. Fluconazole may therefore be more effective for fungal prophylaxis in these patients.

Adolescent↗

No beneficial effect from addition of etoposide to daunorubicin, cytarabine, and 6-mercaptopurine in individualized induction therapy of adult acute myeloid leukemia: the JALSG-AML92 study. Japan Adult Leukemia Study Group.

To assess the efficacy of etoposide added to the standard remission induction therapy for acute myeloid leukemia (AML), newly diagnosed adult AML patients were randomized to receive either daunorubicin (40 mg/m2/day x 4 or more), behenoyl cytarabine (200 mg/m2/day x 10 or more), and 6-mercaptopurine (70 mg/m2/day x 10 or more) (BHAC-DM), or the same three drugs plus etoposide (100 mg/m2/day x 5) (BHAC-EDM) for response-oriented individualized induction therapy. The patients achieving complete remission (CR) received the same 3 courses of consolidation therapy followed by 6 courses of maintenance/intensification therapy. M3 patients were excluded because all-trans retinoic acid was used. Of 667 patients registered, 655 were evaluable. The median age was 49 (range 15 to 85). CR rates were 77% in the BHAC-DM group and 75% in the BHAC-EDM group. In 173 M4 patients, CR rates were 86% and 69% (P = 0.009), and in 32 M5 patients, 80% and 77% (P = 0.810) in the BHAC-DM and the BHAC-EDM groups, respectively. The predicted 6-year overall survival rates were 30% and 38% (P = 0.925) for the BHAC-DM and BHAC-EDM groups, and the disease-free survival rates of CR patients were 25% and 35% (P = 0.352), respectively. Nonhematological toxicities after the first course of induction therapy were almost equal among the two groups, with the exception of a greater loss of hair (P = 0.024) and more frequent diarrhea (P = 0.013) in the BHAC-EDM group. We concluded that in the present study, the addition of etoposide to the standard individualized induction therapy showed no advantage in adult AML, even among M4 and M5 patients.

Acute Disease↗

[Clinical roles of vitamins in hematopoietic disorders].

Vitamins are essential organisms which promote various metabolisms and physiological systems. Several vitamins play important roles in hematopoietic system. Vitamin B12, C and folic acid are associated with DNA synthesis of erythroid nucleus, the deficiency of which causes the megaloblastic anemia. Some megaloblatic anemia and sideroblastic anemia might response to vitamin B1 and B6, respectively. Vitamin K participates in some coagulation factors in coagulation-fibrinogenolysis system. It has been reported that vitamins A, D and K potentially differentiate leukemic cells and then induce the apoptosis, suggesting that they would be new therapeutic agents in acute leukemia.

Anemia↗

Central histaminergic neurons regulate rabbit tracheal tension through the cervical sympathetic nerve.

We previously showed that stimulation of the posterior hypothalamus decreases tracheal tension and involves central histaminergic neurons. In the present study, we reveal that central histaminergic neurons project to the rostral ventrolateral medulla and affect cervical sympathetic nervous activity in rabbits. Administration of histamine into the fourth ventricle increased cervical sympathetic nervous activity and decreased tracheal tension. These effects were inhibited by administration of a histamine H receptor antagonist, pyrilamine, into the fourth ventricle. Unilateral injection of DL-homocysteic acid into the tuberomammillary nucleus increased cervical sympathetic nervous activity, an effect was antagonized by bilateral injection of pyrilamine into the rostral ventrolateral medulla. The pulse correlogram between the stimulation pulse applied to the tuberomammillary nucleus and the cervical sympathetic nerve activity showed a mode at 150 to 200 ms, which was reduced by pyrilamine administration into the fourth ventricle. Fibers anterogradely labeled by Phaseolus vulgaris leucoagglutinin (PHA-L) injected into the tuberomammillary nucleus were distributed in the A1, A2, C1, and C2 areas which are determined by tyrosine hydroxylase-immunohistochemistry. PHA-L positive neurons were in close contact with tyrosine hydroxylase-immunoreactive neurons in these four areas. Cell bodies in the tuberomammillary nucleus retrogradely labeled with fluorogold from the rostral ventrolateral medulla were immunoreactive with histamine. These results suggest that an excitatory efferent pathway projects from the tuberomammillary nucleus to the cervical sympathetic nerve and that the histaminergic neurons of this pathway influence tracheal tension through the rostral ventrolateral medulla.

Animals↗

A novel lipopolysaccharide inducible C-C chemokine receptor related gene in murine macrophages.

To identify genes induced in activated macrophages, we screened a cDNA library prepared from the lipopolysaccharide (LPS)-treated cell line, RAW264, using the suppression subtractive hybridization technique. One of the clones isolated was dramatically induced by LPS in macrophages. The predicted protein sequence of this gene contains the domain unique to seven transmembrane receptors, and shows similarity with mouse C-C chemokine receptor 5 (CCR5). Therefore, we designated it LPS inducible C-C chemokine receptor related gene (L-CCR). Northern blot analysis revealed that L-CCR was specifically expressed in differentiated macrophages after LPS stimulation. These results show that L-CCR is a novel C-C chemokine receptor related gene induced by LPS in macrophages and may play an important role in inflammatory responses.

Amino Acid Sequence↗