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Biomedical subjects

F Kawano

Publications and source records attributed to F Kawano.

At least 19 recordsLinked to original sources

Role(s) of nucleoli and phosphorylation of ribosomal protein S6 and/or HSP27 in the regulation of muscle mass.

Effects of 14 days of hindlimb unloading or synergist ablation-related overloading with or without deafferentation on the fiber cross-sectional area, myonuclear number, size, and domain, the number of nucleoli in a single myonucleus, and the levels in the phosphorylation of the ribosomal protein S6 (S6) and 27-kDa heat shock protein (HSP27) were studied in rat soleus. Hypertrophy of fibers (+24%), associated with increased nucleolar number (from 1-2 to 3-5) within a myonucleus and myonuclear domain (+27%) compared with the preexperimental level, was induced by synergist ablation. Such phenomena were associated with increased levels of phosphorylated S6 (+84%) and HSP27 (+28%). Fiber atrophy (-52%), associated with decreased number (-31%) and domain size (-28%) of myonuclei and phosphorylation of S6 (-98%) and HSP27 (-63%), and with increased myonuclear size (+19%) and ubiquitination of myosin heavy chain (+33%, P > 0.05), was observed after unloading, which inhibited the mechanical load. Responses to deafferentation, which inhibited electromyogram level (-47%), were basically similar to those caused by hindlimb unloading, although the magnitudes were minor. The deafferentation-related responses were prevented and nucleolar number was even increased (+18%) by addition of synergist ablation, even though the integrated electromyogram level was still 30% less than controls. It is suggested that the load-dependent maintenance or upregulation of the nucleolar number and/or phosphorylation of S6 and HSP27 plays the important role(s) in the regulation of muscle mass. It was also indicated that such regulation was not necessarily associated with the neural activity.

Animals↗

Irreversible morphological changes in leg bone following chronic gravitational unloading of growing rats.

Effects of gravitational unloading or loading on the growth and development of hindlimb bones were studied in rats. Male Wistar rats were hindlimb-unloaded or loaded at 2-G from the postnatal day 4 to month 3. The morphology and mineral content of tibia and fibula, as well as the mobility of ankle joints, were measured at the end of 3-month suspension or loading, and 1, 2, and 3 months after ambulation recovery. Growth-related increases of bone weight and mineral density were inhibited by unloading. But they were gradually recovered toward the control levels, even though they were still less than those in the age-matched controls after 3 months. None of the parameters were influenced by 2-G loading. However, here we report that chronic unloading causes abnormal morphological development in hindlimb bone of growing rats. Irreversible external bend of the shaft and rotation of the distal end of tibia, which limit the dorsiflexion of ankle joints, were induced following chronic gravitational unloading during developing period. It is also suggested that such phenomena are caused by the abnormal mechanical forces imposed by muscle utilization with altered patterns. The activity of ankle dorsiflexor was increased and that of plantarflexor was inhibited during unloading.

Animals↗

Mechanical load-dependent regulation of satellite cell and fiber size in rat soleus muscle.

The effects of mechanical unloading and reloading on the properties of rat soleus muscle fibers were investigated in male Wistar Hannover rats. Satellite cells in the fibers of control rats were distributed evenly throughout the fiber length. After 16 days of hindlimb unloading, the number of satellite cells in the central, but not the proximal or distal, region of the fiber was decreased. The number of satellite cells in the central region gradually increased during the 16-day period of reloading. The mean sarcomere length in the central region of the fibers was passively shortened during unloading due to the plantarflexed position at the ankle joint: sarcomere length was maintained at <2.1 microm, which is a critical length for tension development. Myonuclear number and domain size, fiber cross-sectional area, and the total number of mitotically active and quiescent satellite cells of whole muscle fibers were lower than control fibers after 16 days of unloading. These values then returned to control values after 16 days of reloading. These results suggest that satellite cells play an important role in the regulation of muscle fiber properties. The data also indicate that the satellite cell-related regulation of muscle fiber properties is dependent on the level of mechanical loading, which, in turn, is influenced by the mean sarcomere length. However, it is still unclear why the region-specific responses, which were obvious in satellite cells, were not induced in myonuclear number and fiber cross-sectional area.

Animals↗

Allogeneic hematopoietic stem cell transplantation provides sustained long-term survival for patients with adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a distinct peripheral T-cell neoplasm that is highly resistant to chemotherapy. Several groups, including ours, have reported encouraging results of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with ATLL. To confirm our previous report and to establish the basis for a phase II clinical study, we analyzed 40 allo-HSCT for acute and lymphoma types of ATLL in seven institutions in Japan between 1997 and 2002. All evaluable cases entered complete remission (CR) after allo-HSCT and the median survival time was 9.6 months for all patients. The estimated 3-year overall and relapse-free survival, and disease relapse were 45.3, 33.8 and 39.3%, respectively. Among 10 cases with ATLL relapse, five cases achieved CR again: three by the reduction or cessation of immunosuppressive agents, which suggested a graft-versus-ATLL (GvATLL) effect. However, univariate or multivariate analysis did not show any benefit of graft-versus-host disease (GVHD) on the prevention of relapse. These results suggested that allo-HSCT was effective for some patients with aggressive ATLL, and that the GvATLL effect could be achieved even without GVHD. A new phase II trial to test the efficacy of allo-HSCT for ATLL is warranted.

Adult↗

Mutations in the receptor tyrosine kinase pathway are associated with clinical outcome in patients with acute myeloblastic leukemia harboring t(8;21)(q22;q22).

AML1-MTG8 generated by t(8;21) contributes to leukemic transformation, but additional events are required for full leukemogenesis. We examined whether mutations in the receptor tyrosine kinase (RTK) pathway could be the genetic events that cause acute myeloblastic leukemia (AML) harboring t(8;21). Mutations in the second tyrosine kinase domain, juxtamembrane (JM) domain and exon 8 of the C-KIT gene were observed in 10, one and three of 37 AML patients with t(8;21), respectively. Three patients showed an internal tandem duplication in the JM domain of the FLT3 gene. One patient had a mutation in the K-Ras gene at codon 12. As the occurrence of these mutations was mutually exclusive, a total of 18 (49%) patients showed mutations in the RTK pathway. These results suggest that activating mutations in the RTK pathway play a role in part as an additional event leading to the development of t(8;21) AML. The 6-year cumulative incidence of relapse in patients with RTK pathway mutations was 79.8%, compared with 13.5% in patients lacking such mutations (P=0.0029). Furthermore, the 6-year relapse-free survival in patients with mutations was 18% compared to 60% in those without mutations (P=0.0340), indicating that RTK mutations are associated with the clinical outcome in t(8;21) AML.

Adolescent↗

Effects of cold-water immersion on VEGF mRNA and protein expression in heart and skeletal muscles of rats.

AIM: The effects of cold exposure on gene and protein expression of vascular endothelial growth factor (VEGF), in heart and skeletal muscles, were studied in male adult Wistar rats. METHODS: Cold immersion was accomplished by submerging the rats in shoulder-deep water maintained at approximately 18 degrees C, either acutely (1 h) or chronically (1 h day(-1), 5 days week(-1) for 20 weeks). The expressions of VEGF mRNA and protein in heart, gastrocnemius, and soleus muscles were examined by Northern and Western blotting and competitive-polymerase chain reaction techniques. RESULTS: The expressions of VEGF mRNA and protein were markedly increased in cardiac muscle of the cold-immersed group, particularly in the 1-hour exposure group, whereas VEGF mRNA and protein in gastrocnemius were decreased significantly after an acute exposure. Although the protein level in gastrocnemius remained low in the chronically exposed group, the expression of mRNA of VEGF(165) with chronic exposure in this group returned to the control level and that of VEGF(206) was 15% greater than that in controls. The expression of mRNA for VEGF(165) in soleus was also lowered by acute cold exposure, although that for VEGF(206) was stable. However, VEGF protein was increased by 50%. After 20 weeks, all of these parameters were increased over the levels found in the controls. CONCLUSION: These results suggest that the VEGF gene may be a major regulatory factor in cardiac and skeletal muscle adaptation to the cold environment stimulating angiogenesis and thermogenesis.

Actins↗

Tension- and afferent input-associated responses of neuromuscular system of rats to hindlimb unloading and/or tenotomy.

Responses of electromyogram (EMG) in soleus muscle and both afferent and efferent neurograms at the fifth lumbar (L(5)) segmental level of spinal cord were investigated during acute and chronic unloading induced by hindlimb suspension and/or tenotomy in adult rats. The soleus EMG and afferent neurogram decreased 88 and 37%, respectively, relative to those at quadrupedal posture on the floor after acute hindlimb suspension that causes passive shortening of soleus due to ankle plantarflexion. However, the afferent neurogram (P < 0.05) and soleus EMG (P > 0.05) recorded on the floor increased after tenotomy of synergists. Furthermore, the afferent input was inhibited when the soleus EMG disappeared after tenotomy of soleus. The afferent neurogram and EMG of the soleus showed correlated responses to a variety of treatments, suggesting that the afferent neurogram recorded at the L(5) segmental level reflects the neural input associated with the activity level of the soleus predominantly. The level of efferent neurogram decreased after acute hindlimb suspension but was not influenced significantly by tenotomy of synergists and/or soleus itself. The EMG and afferent neurograms remained low up to the 4th day but recovered to the preexperimental levels within 14 days, due to reorganization of sarcomere number and length, as well as the shortening of muscle fiber length and recovery of tension development. It is suggested that the levels of EMG and afferent neurogram associated with antigravity muscle are closely related to the tension development of the muscle.

Animals↗

Hindlimb suspension inhibits air-righting due to altered recruitment of neck and back muscles in rats.

Effects of 9-week hindlimb suspension and 8-week recovery on air-righting reaction in response to drop from a supine position were studied in adult rats. The righting time in rats at the end of suspension (approximately 220 ms) was longer than the age-matched controls (approximately 120 ms, p <0.05). The unloading-related change in righting time was accompanied by lowered activities of electromyogram (EMG) and altered recruitment of both neck and back muscles at a specific stage of drop. After 8 weeks of reambulation, righting time recovered toward the control level (approximately 153 ms, p <0.05), but the EMG activity of back muscle was still less than controls. In contrast, the EMG of neck muscle during fall was even increased. The differences in the characteristics of the muscle fibers between two groups were minor. It is suggested that inhibition of recruitment, rather than the changes in the fiber characteristics, of neck and back muscles is one of the major causes of the slow air-righting.

Adaptation, Physiological↗

Effects of 20-week intermittent cold-water-immersion on phenotype and myonuclei in single fibers of rat hindlimb muscles.

The effects of 20 weeks of intermittent cold-water-immersion on myosin heavy chain (MHC) expression,cross-sectional area (CSA), myonuclear number, and myonuclear domain size in isolated single fiber of soleus and extensor digitorum longus (EDL) muscles were studied in male Wistar rats. Cold exposure was accomplished by submerging the rats in shoulder-deep water, maintained at approximately 18 degrees C, for 1 hour/day, 5 days/week and for 20 weeks. Cold exposure resulted in a significant inhibition of body and soleus muscle weight gain. The percent type IIa MHC fibers of EDL muscle was increased, whereas that of type IIa + b MHC fibers was less in cold-exposed group than controls (p < 0.05). The mean CSA and myonuclear number in type I MHC fibers of soleus muscle in cold-exposed group were significantly less than controls. Myonuclear domain in type IIa fibers of EDL in the cold-exposed group was greater than controls (p < 0.05). It is suggested that prolonged cold exposure causes the fiber-type-specific adaptation in rat hindlimb muscles. It is further indicated that cold-exposure-related modulation of myonuclear number was closely related to reduction of fiber CSA, not the shift of fiber phenotype.

Animals↗

[Ruptured aortic arch aneurysm with hemorrhagic cardiac tamponade; report of a case].

The ruptured aortic arch aneurysm with cardiac tamponade is rare and has severely high mortality. We report a case of ruptured aortic arch aneurysm with cardiac tamponade. A 66-year-old man who had syncope attack was transferred to city hospital. Brain computed tomography (CT) showed no significant lesion and he admitted to our hospital for suspecting of aortic dissection. Chest CT showed ruptured aortic arch aneurysm and pericardial effusion. Emergent operation was done on the same day. It was found that the hematoma beneath the tunica adventitia existed at the distal arch and extended to the ascending aorta. Cardiac tamponade was caused by rupture of subadventitial hematoma in pericardial space. Aortic arch replacement was performed using selective cerebral perfusion under deep hypothermia. Postoperatively, he had no cerebral complication and was discharged uneventfully.

Aged↗

Effects of aging and exercise on density and cross-sectional area of femur in senescence-accelerated mouse prone 6.

The densities and cross-sectional areas (CSAs) of the femur in 40- and 60-week-old senescence-accelerated mice prone 6 (SAMP6) were determined using peripheral quantitative computed tomography (pQCT) and compared with those in age-matched control mice (ICR). In addition, the effects of 20 weeks of voluntary running exercise with increasing loads on femur density and CSA were examined in SAMP6. There were no differences in the cortical and trabecular densities or CSAs between the 40- and 60-week-old ICR. The cortical and trabecular densities of the 60-week-old control SAMP6 were lower than those of the 40-week-old control SAMP6. There was no difference in the cortical CSA between the 40- and 60-week-old control SAMP6, while the trabecular CSA of the 60-week-old control SAMP6 was higher than that of the 40-week-old control SAMP6. It was concluded that an age-related decline in femur cortical and trabecular densities occurs at an earlier age in control SAMP6, indicating that SAMP6 show accelerated progression of age-associated osteoporosis. There were no differences in the cortical density between the 40-week-old control and 60-week-old exercised SAMP6. These data indicate that running exercise with increasing loads prevents age-associated osteoporosis in this senescence-accelerated mouse strain.

Journal Article↗

Cefepime or carbapenem treatment for febrile neutropenia as a single agent is as effective as a combination of 4th-generation cephalosporin + aminoglycosides: comparative study.

1998, a consensus meeting was held in Miyazaki, Japan, to develop an approach to management of febrile neutropenia (FN). The K-HOT study group decided to examine whether this proposal was applicable to clinical practice in a multicenter study. Patients who developed fever with neutrophil counts <1,000/microL were randomized to receive either a single antibiotic, cefepime or one of the carbapenems, or a combination of cefepime and an aminoglycoside. Patients who became afebrile within the first 3 days were continued on the same treatment. Patients who remained febrile were switched to a combination regimen if they were randomized to receive a single agent, and patients on combination medication were changed from cefepime to another cephalosporin. A total of 165 patients were entered into the trial. One hundred fifty-three patients were evaluable for response. The average age was 52 years, and 70% of the patients had acute leukemia. Severe neutropenia, defined as <100/microL at the time of FN, was seen in 62% of the patients on entry and during the course of treatment 71% of patients experienced neutrophil counts of <100/microL. Microbiologically documented infection was seen in 6.5% for monotherapy, and 10.5% for a combination treatment, and fever of unknown origin occurred in 75.3% and 59.2% of the patients in each regimen, respectively. Excellent to good response was seen in two-thirds of the patients in all treatment groups. Adverse events were minimal, and three early deaths were observed at days 9, 16, and 16 among patients treated with a single antibiotic and three in the combination regimen group at days 14, 15, and 20. These results indicate that cefepime or a carbapenem alone is as effective as a combination of cefepime and an aminoglycoside for treating FN.

Adult↗

Gravitational unloading effects on muscle fiber size, phenotype and myonuclear number.

The effects of gravitational unloading with or without intact neural activity and/or tension development on myosin heavy chain (MHC) composition, cross-sectional area (CSA), number of myonuclei, and myonuclear domain (cytoplasmic volume per myonucleus ratio) in single fibers of both slow and fast muscles of rat hindlimbs are reviewed briefly. The atrophic response to unloading is generally graded as follows: slow extensors > fast extensors > fast flexors. Reduction of CSA is usually greater in the most predominant fiber type of that muscle. The percentage of fibers expressing fast MHC isoforms increases in unloaded slow but not fast muscles. Myonuclear number per mm of fiber length and myonuclear domain is decreased in the fibers of the unloaded predominantly slow soleus muscle, but not in the predominantly fast plantaris. Decreases in myonuclear number and domain, however, are observed in plantaris fibers when tenotomy, denervation, or both are combined with hindlimb unloading. All of these results are consistent with the view that a major factor for fiber atrophy is an inhibition or reduction of loading of the hindlimbs. These data also indicate that predominantly slow muscles are more responsive to unloading than predominantly fast muscles.

Animals↗

Afferent input-associated reduction of muscle activity in microgravity environment.

Responses of electromyogram (EMG) of soleus, lateral portion of gastrocnemius (LG) and tibialis anterior (TA), and both afferent and efferent neurograms at the L(5) segmental level of the spinal cord, to altered gravity levels created by the parabolic flight of a jet airplane were investigated in adult rats. The EMG activity in antigravity soleus muscle gradually increased when the gravity was elevated from 1-G to 1.5-G (+23%) and 2-G (+67%) during the ascending phase of parabolic flight. The activity decreased approximately 72% from the 1-G level immediately when the rat was exposed to microgravity. The EMG level was maintained low during the 20-s microgravity, but it was restored immediately once the gravity level was increased to 1.5-G and then 1-G during the descending and recovery phase. The EMG level of LG also increased gradually when the gravity level was elevated and the level then decreased when the rat was exposed to microgravity (P>0.05). However, the activity level during the 20-s microgravity was identical to that obtained at 1-G. The EMG level of TA even increased insignificantly in response to the exposure to microgravity. The responses of afferent neurogram were similar to those of soleus EMG, even though the magnitude of the reduction of integrated neurogram level in response to microgravity exposure was small (approximately 26% vs. 1-G level) relative to that of soleus EMG. The level of efferent neurogram was also decreased, but only approximately 9% vs. 1-G level, during the 20-s microgravity. The data in the current study suggest that the afferent input is closely associated with the gravity-dependent muscular activity.

Aircraft↗

Randomized phase II study of biweekly CHOP and dose-escalated CHOP with prophylactic use of lenograstim (glycosylated G-CSF) in aggressive non-Hodgkin's lymphoma: Japan Clinical Oncology Group Study 9505.

BACKGROUND: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) is accepted as the best available standard treatment for first-line chemotherapy in aggressive non-Hodgkin's lymphoma (NHL). However, the therapeutic efficacy of CHOP remains unsatisfactory, particularly in high-intermediate risk and high risk patients, and a new strategy is warranted in this patient population. The aim of the present study was to explore a suitable therapeutic-intensified regimen for the treatment of aggressive NHL. PATIENTS AND METHODS: Between May 1995 and July 1998, a total of 70 patients with high-intermediate risk or high risk aggressive NHL, according to the International Prognostic Index, were enrolled and randomly assigned to receive either eight cycles of standard CHOP (cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.4 mg/m(2) and prednisolone 100 mg for 5 days) every 2 weeks, or six cycles of dose-escalated CHOP (cyclophosphamide 1500 mg/m(2), doxorubicin 70 mg/m(2), vincristine 1.4 mg/m(2) and prednisolone 100 mg for 5 days) every 3 weeks. Lenograstim (glycosylated rHuG-CSF), at a dose of 2 micro g/kg/day s.c., was administered daily from day 3 until day 13 with biweekly CHOP and until day 20 with the dose-escalated CHOP. The primary endpoint was complete response rate. RESULTS: The complete response rate was 60% [21 of 35; 95% confidence interval (CI) 42% to 76%] with biweekly CHOP and 51% (18 of 35; 95% CI 34% to 69%) with dose-escalated CHOP. The major toxicity was grade 4 neutropenia and was more frequent in the dose-escalated CHOP arm (86%) than in the biweekly CHOP arm (50%). Grade 4 thrombocytopenia was also more frequent in the dose-escalated CHOP arm (20%) than the biweekly CHOP arm (3%). Non-hematological toxicities were acceptable in both arms. One treatment-related death (due to cardiac arrhythmia) was observed in a dose-escalated CHOP patient. Progression-free survival at 3 years was 43% (95% CI 27% to 59%) in the biweekly CHOP arm and 31% (95% CI 16% to 47%) in the dose-escalated CHOP arm. Although seven patients were deemed ineligible by central review of the pathological diagnosis, the results for both eligible and all enrolled patients were similar. CONCLUSIONS: Similar complete response rates and progression-free survival rates, but lower toxicity, indicated that biweekly CHOP was superior to dose-escalated CHOP in the treatment of aggressive NHL. Based on these results, the Lymphoma Study Group of the Japan Clinical Oncology Group is conducting a randomized phase III study comparing biweekly CHOP with standard CHOP in newly diagnosed patients with advanced-stage aggressive NHL.

Adult↗

Enhanced Hoffman-reflex in human soleus muscle during exposure to microgravity environment.

Responses of Hoffman-reflex in the soleus muscle to changes of gravity levels created by parabolic flight of a jet airplane were investigated in four healthy male subjects. The subjects maintained a sitting position with seat belts fastened, keeping the anterior ankle and posterior knee angles at approximately 135 degrees. The gravity levels were altered from 1- to 2-G, and then microgravity was created for approximately 20 s. The levels were recovered from 1.5- to 1-G during the descending phase. The time interval between the stimulation and either M- or H-wave was not influenced by the changes in gravity levels. The amplitude of the M-wave during hyper- and microgravity was identical to that obtained at 1-G. However, the H-wave amplitude was increased when the subjects were exposed to microgravity (approximately four times vs. 1-G level). The H/M ratio was also elevated during microgravity. Further, such a phenomenon was maintained throughout the 20 s of microgravity exposure. Hypergravity at 1.5- or 2-G had no effect on the H-wave amplitude. It is suggested that an acute exposure to microgravity increases the excitability of the soleus motor pool and the increased excitability is restored immediately when the gravity level is elevated.

Adult↗

Reinforcement effect of short glass fibers with CaO- P(2)O(5) -SiO(2) -Al(2)O(3) glass on strength of glass-ionomer cement.

OBJECTIVES: A high strength glass-ionomer (not resin-modified) cement was developed using short fibers of CaO--P(2)O(5)--SiO(2)--Al(2)O(3) (CPSA) glass. The purpose of this study was to clarify the effect of the CPSA short fibers contained in the flexural strength of the glass-ionomer cement. METHOD: The 40 mass% short fibers of CPSA glass were added to the powder of commercial glass-ionomer cement. Beam specimens of set cement (25 x 2 x 2 mm) were prepared for measuring the flexural strength (FS). The specimens of set commercial glass-ionomer cement (GI) were used for comparison with glass ionomer cement with CPSA (FRGI). Half of all specimens were thermocycled in water for 60s of dwell time at 4 and 60 degrees C for 2500, 5000, and 10,000 cycles. The other specimens were stored in water at 37 degrees C as a control. The measurements were statistically analyzed using ANOVA. RESULTS: The initial FS of FRGI was 18.1 and that of GI was 7.7 MPa. After thermocycling, the mean FS ranged from 19.3 to 26.3 MPa and 9.8 to 11.1 MPa for FRGI and GI, respectively. After storage in water, the mean FS of FRGI and GI ranged from 20.4 to 25.9 MPa and 9.4 to 10.1 MPa, respectively. CONCLUSION: These findings suggested that glass-ionomer cement reinforced with CPSA short fibers maintains a higher strength than the conventional cement after aging.

Analysis of Variance↗

Isolation and characterization of methicillin-resistant Staphylococcus aureus strains from nares of nurses and their gowns.

The isolation and characterization of methicillin-resistant Staphylococcus aures (MRSA) strains from the bilateral nares of nurses and their gowns are described. MRSA strains could be isolated from eigth of fifty bilateral nares of nurses and two of their gowns. Ten MRSA strains were typed using coagulase typing, and divided into two types, coagulase II and III. In this study, we found a new group (producing toxic shock syndrome toxin -1, coagulase III and staphylococcal enterotoxin C) in Japanese MRSA. Furthermore, we confirmed that MRSA strains originating from bilateral nares of three nurses were identical and two strains isolated from the left naris of one nurse and her gown were also identical by pulsed-field gel electrophoresis.

Bacterial Toxins↗