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Biomedical subjects

K Kubo

Publications and source records attributed to K Kubo.

At least 19 recordsLinked to original sources
PubMed2006

Elongation/compaction of giant DNA caused by depletion interaction with a flexible polymer.

Structural changes in giant DNA induced by the addition of the flexible polymer Polyethylene Glycol (PEG) were examined by the method of single-DNA observation. In dilute DNA conditions, individual DNA assumes a compact state via a discrete coil-globule transition, whereas in concentrated solution, DNA molecules exhibit an extended conformation via macroscopic phase segregation. The long-axis length of the stretched state in DNA is about 10(3) times larger than that of the compact state. Phase segregation at high DNA concentrations occurs at lower PEG concentrations than the compaction at low DNA concentrations. These opposite changes in the conformation of DNA molecule are interpreted in terms of the free energy, including depletion interaction.

Bacteriophage T4↗
PubMed2006

Effects of nifedipine and interleukin-1alpha on the expression of collagen, matrix metalloproteinase-1, and tissue inhibitor of metalloproteinase-1 in human gingival fibroblasts.

BACKGROUND AND OBJECTIVE: Nifedipine-induced gingival overgrowth is known to be characterized by fibrosis and some degree of inflammation. However, the molecular mechanism of the fibrosis is not fully understood. The purpose of this study was to investigate in vitro the effects of nifedipine and interleukin-1alpha on the molecules involved in fibrosis, namely type I collagen, matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1). MATERIAL AND METHODS: Four human gingival fibroblast strains, derived from four healthy volunteers, were cultured in media containing nifedipine (1 microg/ml), with or without interleukin-1alpha (0.05 ng/ml). The mRNAs of type I collagen, MMP-1, and TIMP-1 were measured by reverse transcription-polymerase chain reaction (RT-PCR). The proteins of MMP-1 and TIMP-1 were examined by enzyme-linked immunosorbent assay (ELISA), and the ratios of MMP-1 to TIMP-1 proteins were calculated. RESULTS: The mRNA expression of type I collagen showed no significant change. Both mRNA expression and protein production of MMP-1 were up-regulated by interleukin-1alpha, either alone or in combination with nifedipine, whereas those of TIMP-1 were up-regulated by nifedipine alone or in combination with interleukin-1alpha. The ratio of MMP-1 to TIMP-1 was not changed by nifedipine alone, but it was increased by interleukin-1alpha alone or in combination with nifedipine. However, in two of the four cell strains tested, nifedipine reduced the ratio of MMP-1 to TIMP-1 compared with that for interleukin-1alpha alone. CONCLUSION: These results suggest that nifedipine may predispose to fibrosis in some individuals in situations where interleukin-1 levels are raised.

Adolescent↗
PubMed2006

Effects of isometric training at different knee angles on the muscle-tendon complex in vivo.

The purpose of this study was to investigate the influences of isometric training at different joint angles on the muscle size and function of the human muscle-tendon complex in vivo. Furthermore, we tried to gain a better understanding of the mechanisms involved in angle specificity after isometric training from the aspect of neuromuscular adaptation and the changes in the properties of the muscle-tendon complex. Nine males completed 12-week unilateral training program (70% of maximal voluntary contraction (MVC) x 15 s x six sets) on the knee extensors at 50 degrees (shorter muscle length: ST) and 100 degrees (longer muscle length: LT). The internal muscle force (mechanical stress) is higher at 100 degrees than at 50 degrees because of the difference in the moment arm length, although there were no difference in the relative torque level, contraction and relaxation times, and repetition between ST and LT. Before and after training, isometric strength at eight angles and muscle volume were determined. Tendon elongation of knee extensors was measured by ultrasonography. There was no significant difference in the rate of increment of muscle volume between the protocols. Tendon stiffness increased significantly for LT, but not for ST. Although significant gain was limited to angles at or near the training angle for ST, increases in MVC at all angles were found for LT. These results suggest that only mechanical stress (internal muscle force imposed on muscle and tendon) contributes to adaptation in the tendon stiffness, although metabolic (relative torque level, etc.) and mechanical stress relate to muscle hypertrophy. Furthermore, increment of tendon stiffness for LT might contribute to increase torque output at smaller angles other than the training angle.

Adaptation, Physiological↗
PubMed2006

Responses of rat pulp cells to heat stress in vitro.

Although heat stress can cause irritation in the dentin/pulp complex, little is known about the thermotolerance of pulp cells and their response to heat stress. We investigated cultured rat pulp cell responses to heat stress. Cells were subjected to a temperature of 42 degrees C for 30 minutes, and HSPs, alkaline phosphatase activity, and gap-junctional communication were determined at various time points. Although only low levels of HSP70 expression were detected before heat treatment, heat shock markedly induced HSP70 expression, with it gradually increasing at 1 hour after being heated. HSP25, however, showed no dramatic change. Gap junction protein connexin43 rapidly degraded after heat treatment, recovering to normal levels within the following 6 hours. Alkaline phosphatase activity decreased immediately after heat stress, recovering after 1 hour. These results indicate that dental pulp possesses protective factors, including HSPs, and that it can recover viability of intercellular communication and alkaline phosphatase activity after heat stress.

Alkaline Phosphatase↗
PubMed2006

Percutaneous radio-frequency mandibular nerve rhizotomy guided by CT fluoroscopy.

We describe a new method for radio-frequency mandibular nerve rhizotomy under CT fluoroscopy. A patient with cancer had severe intractable and drug-resistant pain in his left mandibular region. Because he had an anatomic deformity due to cancer invasion and radiation therapy, we planned a mandibular nerve rhizotomy under CT fluoroscopic imaging. The needle was advanced to the mandibular nerve just caudal to the foramen ovale under real-time CT fluoroscopy, avoiding the cancer region. Pain scores of the patient were reduced after the nerve rhizotomy, without any complications.

Catheter Ablation↗
PubMed2005

High dose of Garcinia cambogia is effective in suppressing fat accumulation in developing male Zucker obese rats, but highly toxic to the testis.

We investigated the ability of Garcinia cambogia extract containing (-)-hydroxycitric acid (HCA) to suppress body fat accumulation in developing male Zucker obese (fa/fa) rats. We also examined histopathologically the safety of its high doses. Diets containing different levels of HCA (0, 10, 51, 102 and 154 mmol/kg diet) were fed to 6-week-old rats for 92 or 93 days. Each diet group was pair-fed to the 154 mmol HCA/kg diet group. Epididymal fat accumulation and histopathological changes in tissues were observed. The highest dose of HCA-containing Garcinia cambogia (154 mmol HCA/kg diet) showed significant suppression of epididymal fat accumulation in developing male Zucker obese rats, compared with the other groups. However, the diets containing 102 mmol HCA/kg diet and higher (778 and 1244 mg HCA/kg BW/d, respectively) caused potent testicular atrophy and toxicity, whereas diets containing 51 mmol HCA/kg diet (389 mg HCA/kg BW/d) or less did not. Accordingly, 51 mmol HCA/kg diet (389 mg HCA/kg BW/d) was deemed to be the no observed adverse effect level (NOAEL).

ATP Citrate (pro-S)-Lyase↗
PubMed2005

Identification of Ki23819, a highly potent inhibitor of kinase activity of mutant FLT3 receptor tyrosine kinase.

Constitutively active internal tandem duplication (ITD) in the juxtamembrane domain of Fms-like tyrosine kinase 3 (FLT3), a type III receptor tyrosine kinase, is the most common molecular defect associated with acute myeloid leukemia. Its presence confers a poor outcome in patients with acute myeloid leukemia who receive conventional chemotherapy. FLT3-ITD has therefore been considered to be an attractive molecular target for a novel therapeutic modality. We describe here the identification and characterization of Ki23819 as a novel FLT3 inhibitor. Ki23819 suppressed proliferation and induced apoptosis of FLT3-ITD-expressing human leukemia cell lines. The growth-inhibitory effect of Ki23819 on MV4-11 cells was superior to that of SU11248, another FLT3 inhibitor (IC(50)<1 vs 3-10 nM). Ki23819 inhibited the autophosphorylation of FLT3-ITD more efficiently than that of wild-type FLT3. FLT3-ITD-dependent activation of the downstream signaling proteins ERK and STAT5 was also inhibited within similar concentration ranges. Thus, Ki23819 is a potent in vitro inhibitor of FLT3.

Acute Disease↗
PubMed2005

Trial of remote telemedicine support for patients with chronic respiratory failure at home through a multistation communication system.

To create and test a multistation telemedicine support system, three remote locations were connected: the homes of two patients with chronic respiratory failure, the hospital of the attending physician, and the hospital of the pulmonary specialist. Real-time connections were set up between the three locations. Medical history and biologic variables were noninvasively recorded, including blood pressure, arterial oxygen saturation, three-lead electrocardiogram, and end-tidal carbon dioxide. Both physicians shared in these data real-time. If necessary, the respiratory specialist could provide medical advice to the attending physician based on the patient's condition. The trial program resulted in the same information being exchanged remotely using the multi-station telemedicine system that would be exchanged in a direct, face-to-face encounter. This result, together with the improvement in quality of life and the establishment of appropriate treatment and cooperation between the respiratory specialist and attending physician, suggests our system can be considered useful and promising for further use.

Aged↗
PubMed2005

HLA class II DPB1, DQA1, DQB1, and DRB1 genotypic associations with occupational allergic cough to Bunashimeji mushroom.

We previously reported that two-third of workers in a Bunashimeji mushroom (Hypsizigus marmoreus) farm complained of respiratory allergic symptoms, but one-third workers did not suffer from such symptoms even when working for a long period. CD4+ T-helper (Th) cells increased, and Th2/Th1 ratio increased in the allergic workers. To address these immunological backgrounds, we have investigated whether there is any relationship between mushroom allergy and human leukocyte antigen (HLA) class II alleles of DPB1, DQA1, DQB1, and DRB1 by using the polymerase chain reaction-restriction fragment length polymorphism (RFLP) and sequencing-based typing methods. We observed that the allele frequencies of DQA1*0103, DQB1*0601, and DRB1*0803 were significantly higher in the workers having no allergic symptoms than allergic workers (DQA1*0103: 57 vs 25%, DQB1*0601: 49 vs 14%, and DRB1*0803: 29 vs 0%). However, this phenomenon was not seen in workers producing another kind of mushroom, Honshimeji (Lyophyllum aggregatum). The HLA-DRB1*0803 allele alone, the DRB1*0803, DQA1*0103, DQB1*0601 haplotype, or both were negatively associated with allergy to Bunashimeji, and these alleles might be involved in the prevention of Bunashimeji mushroom-specific respiratory allergy.

Adult↗
PubMed2005

Phase I trial of nedaplatin and paclitaxel for patients with non-small cell lung cancer.

A phase I study was conducted to evaluate the maximum tolerated dose and feasibility of combination with nedaplatin (NDP) and paclitaxel in patients with non-small cell lung cancer (NSCLC). Fifteen patients under 75 years old, with unresectable NSCLC who had not previously received chemotherapy or radiotherapy, with a performance status of 0-1, were enrolled. The dose escalation levels (NDP/Paclitaxel; mg/m2 day 1) were 80/150 (level 1), 80/180 (level 2), 90/180 (level 3) and repeated every 28 days. All patients receiving level 3 had dose-limiting toxicity. One patient developed grade 4 neutropenia with infection, two had incomplete recovery of neutropenia and thrombocytopenia by the 28th day after the first cycle of chemotherapy. Non-hematologic toxicities, including nephrotoxicity, nausea/vomiting, alopecia, and hypersensitivity reaction, were tolerated. Three of the 15 patients achieved partial responses. We concluded that the recommended dose was paclitaxel 180 and NDP 80 mg/m2 due to the hematologic toxicity.

Adult↗
PubMed2005

Airway inflammation during stable and acutely exacerbated chronic obstructive pulmonary disease.

The aim of this study was to clarify the mechanism of increased airway inflammation during an acute exacerbation. A total of 68 chronic obstructive pulmonary disease patients in a stable phase were enrolled and followed-up for 2-3 yrs. Inflammatory cells were analysed, and interleukin (IL)-8, neutrophil elastase, eotaxin, tryptase and RANTES (regulated on activation, normal T-cell expressed and secreted) were measured in sputum, both in a stable phase and during acute exacerbation. Out of 68 patients, 30 (unstable group) developed an acute exacerbation and expectorated adequate sputum during exacerbation. Thirty-two patients (stable group) did not develop any exacerbation for 2-3 yrs. The number of neutrophils, lymphocytes and eosinophils, and the levels of IL-8, eosinophil cationic protein (ECP), eotaxin and tryptase in sputum obtained from patients in both groups during the stable phase were significantly higher than those from healthy nonsmokers. There were no significant differences in cell analysis and biomarkers between the two groups, but patients in the unstable group showed more severe airflow limitation. In the unstable group, total cells, lymphocytes, neutrophils and eosinophils, and IL-8, neutrophil elastase, ECP and RANTES levels were significantly increased during an exacerbation from values in a stable phase. These findings suggest that exacerbation of chronic obstructive pulmonary disease may associate with additional increases in airway inflammation mediated by neutrophils, lymphocytes, eosinophils, interleukin-8 and RANTES.

Acute Disease↗
PubMed2005

Antiproteinuric effect of ARB in lupus nephritis patients with persistent proteinuria despite immunosuppressive therapy.

Recent immunosuppressive treatments for lupus nephritis have improved renal survival rate, however, there still exists lupus nephritis refractory to these treatments. Angiotensin receptor blockers (ARBs) are known not only to decrease blood pressure but also to have an independent renoprotecting effect by interrupting renin-angiotensin system. The aim of this study was to evaluate whether ARBs have an additive effect on refractory lupus nephritis. Enrolled in this trial were twelve patients with lupus nephritis who were diagnosed by renal biopsy and remained proteinuria despite corticosteroids and/or immunosuppressive treatments. ARB, losartan or candesartan, was administered for six months. Various clinical parameters were compared before and after ARB administration. Proteinuria decreased after ARB treatment in 83% of the patients and the median amount of proteinuria significantly decreased from 2530 mg/g Cr to 459 mg/g Cr (P = 0.03). In addition, serum albumin and cholesterol levels were significantly improved. Systolic blood pressure significantly decreased, but none had symptoms of hypotension. The antiproteinuric effect of ARB did not correlate with the reduction of blood pressure. Interestingly, higher total complement activity levels before ARB treatment were associated with a greater reduction of proteinuria. The addition of ARB would be a safe and effective treatment for lupus nephritis with persistent proteinuria despite corticosteroids and/or immunosuppressive treatments.

Adult↗
PubMed2004

Achievement of ultralow emittance beam in the accelerator test facility damping ring.

For high luminosity in electron-positron linear colliders, it is essential to generate low vertical emittance beams. We report on the smallest vertical emittance achieved in single-bunch-mode operation of the Accelerator Test Facility, which satisfies the requirement of the x-band linear collider. The emittances were measured with a laser-wire beam-profile monitor installed in the damping ring. The bunch length and the momentum spread of the beam were also recorded under the same conditions. The smallest vertical rms emittance measured at low intensity is 4 pm at a beam energy of 1.3 GeV, which corresponds to the normalized emittance of 1.0x1.0(-8) m. It increases by a factor of 1.5 for a bunch intensity of 10(10) electrons. The measured data agreed to the calculation of intrabeam scattering within much better than a factor of 2.

Journal Article↗
PubMed2004

Effects of 20 days of bed rest on the viscoelastic properties of tendon structures in lower limb muscles.

OBJECTIVES: The purpose of this study was to investigate the effects of 20 days' bed rest on the viscoelastic properties of human tendon structures in knee extensor and plantar flexor muscles in vivo. METHODS: Eight healthy men (age: 24+/-4 years, height: 172+/-9 m, body mass: 69+/-13 kg) carried out a 6 degrees head-down bed rest for 20 days. Before and after bed rest, elongation (L) of the tendon and aponeurosis of vastus lateralis (VL) and medial gastrocnemius muscles (MG) during isometric knee extension and plantar flexion, respectively, were determined using real-time ultrasonic apparatus, while the subjects performed ramp isometric contraction up to the voluntary maximum, followed by ramp relaxation. The relationship between estimated muscle force (Fm) and tendon elongation (L) was fitted to a linear regression, the slope of which was defined as stiffness. The hysteresis was calculated as the ratio of the area within the Fm-L loop to the area beneath the load portion of the curve. RESULTS: L values above 100 N were significantly greater after bed rest for VL, while there were no significant differences in L values between before and after for MG. The stiffness decreased after bed rest for VL (70.3+/-27.4 v 50.1+/-24.8 N/mm, before and after bed rest, respectively; p = 0.003) and MG (29.4+/-7.5 v 25.6+/-7.8 N/mm, before and after bed rest, respectively; p = 0.054). In addition, hysteresis increased after bed rest for VL (16.5+/-7.1% v 28.2+/-12.9%, before and after bed rest, respectively; p = 0.017), but not for MG (17.4+/-4.4% v 17.7+/-6.1%, before and after bed rest, respectively; p = 0.925). CONCLUSIONS: These results suggested that bed rest decreased the stiffness of human tendon structures and increased their hysteresis, and that these changes were found in knee extensors, but not the plantar flexors.

Adult↗
PubMed2003

Systemic lupus erythematosus and thrombotic thrombocytopenic purpura: a case report and literature review.

We describe a patient with systemic lupus erythematosus (SLE) who developed severe and acute thrombotic thrombocytopenic purpura (TTP). Detection of the fragmentation of peripheral red blood cells (RBC) helped the early diagnosis of TTP and the patient was rescued by extensive plasma exchange started promptly after the diagnosis. Because manifestations of TTP are similar to those in SLE, it is sometimes difficult to make an accurate diagnosis of TTP in SLE patients. We emphasise here the significance of the early diagnosis of TTP by the observation of fragmented RBC and the intensive therapy, including plasma exchange, for this very severe condition.

Adult↗
PubMed2003

Prolonged effects of polyriboinosinic:polyribocytidylic acid on spontaneous running wheel activity and brain interferon-alpha mRNA in rats: a model for immunologically induced fatigue.

Following 2 weeks acclimation to the running wheel in the home cages, an i.p. injection of a synthetic double-stranded RNA, polyriboinosinic:polyribocytidylic acid (poly I:C, 3 mg/kg), was performed to produce the immunologically induced fatigue in rats. The daily amounts of spontaneous running wheel activity decreased to about 40-60% of the preinjection level until day 9 with normal circadian rhythm, then gradually returned to the baseline level by day 14. Rats given a heat exposure (36 degrees C for 1 h) for the consecutive 3 days showed an increase in activity except for the first day. In the open field test, the total moving distance and the number of rearing of the poly I:C-injected rats decreased on day 1, but they were not different from the saline-injected group on day 7, suggesting that the poly I:C-induced fatigue on day 7 was not due to the peripheral problems such as muscle/joint pain, but involved the CNS. Quantitative analysis of mRNA levels using a real-time capillary reverse transcriptase-polymerase chain reaction (RT-PCR) method revealed that interferon-alpha (IFN-alpha) mRNA contents in the cortex, hippocampus, hypothalamic medial preoptic, paraventricular, and ventromedial nuclei were higher in the poly I:C group than those in the saline and heat-exposed groups on day 7, although the amount of interleukin-1 beta mRNA showed no differences. Serum adrenocorticotropic hormone and catecholamine levels were not significantly different between groups. The present results indicate that the prolonged fatigue induced by poly I:C, which is evaluated by the spontaneous running wheel activity, can be used as an animal model for the immunologically induced fatigue associated with viral infection, and suggest that brain IFN-alpha may play a role in this model.

Adrenocorticotropic Hormone↗
PubMed2003

Human papillomaviruses in the normal oral cavity of children in Japan.

The purpose of this study was to determine the frequency of human papillomavirus (HPV) infections in the normal oral cavity of children in Japan. Oral squamous cell specimens were collected from 77 children (44 boys and 33 girls), aged 3 and 5 years. Extracted DNA was evaluated for HPV infections by polymerase chain reaction (PCR) methods, using consensus primers for the L1 region, specific primers, and direct DNA sequencing analysis. Thirty-seven of 77 specimens (48.1%) were positive for HPV DNA. Positive rates of boys and girls in all specimens were 28.3 (22/77) and 19.5 (15/77)%, respectively. The positive rate in 3-year-old children was 45.2 (14/31)%, and positive rates in boys and girls were 52.6 (10/19) and 33.3 (4/12)%, respectively. The positive rate in 5-year-old children was 50.0 (23/46)%, and positive rates in boys and girls were 48.0 (12/25) and 52.4 (11/21)%, respectively. HPV types were determined by specific PCR and direct DNA sequencing analysis. Frequent HPV types in the specimens of all children were HPV-16 (11/37; 29.7%),-1 (6/37; 16.2%),-2 (6/37; 16.2%),-75 (6/37; 16.2%). The results of the present investigation indicate that many HPVs, including HPV-16 (a high-risk type for cancer), are present in the oral cavity of 3- and 5-year-old children. It is suggested, therefore, that the oral cavity is already a reservoir of HPVs in childhood where later HPV-associated diseases, such as oral cancer and other oral lesions, may develop.

Age Distribution↗