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Biomedical subjects

K Sakamoto

Publications and source records attributed to K Sakamoto.

At least 109 records · Page 6Linked to original sources

Phase Ia study of a hypoxic cell sensitizer doranidazole (PR-350) in combination with conventional radiotherapy.

A phase Ia study of a 2-nitroimidazole nucleoside analog radiosensitizer doranidazole was conducted to evaluate its toxicity and pharmacokinetics in patients undergoing conventional external beam radiotherapy. Twenty-nine patients, aged 40-74 years, with a WHO performance status of 0-2 and with adequate organ functions, were entered in the study. Single administration of doranidazole was investigated first with 13 patients and then a course of five consecutive daily administrations was tested in 16 patients. Doranidazole was given i.v. 25 min before irradiation. Doranidazole doses of 400, 800, 1300 and 2000 mg/m2 were evaluated in the former study, and daily doses of 800, 1300 and 2000 mg/m2 were investigated in the latter study. All patients tolerated doranidazole administration. Although a transient decrease in the 24-h creatinine clearance rate was observed in five patients (one in the single administration study and four in the repeat administration study), this was not considered to be the dose-limiting toxicity. Other toxicities (hematological and gastrointestinal), which may not be related to doranidazole administration, were also mild and were not dose limiting. No neurotoxicity was observed. The average maximum concentration, area under the time-concentration curve and half-life of doranidazole in serum were 172-194 microg/ml, 502-582 microg x h/l and 4.2-4.6 h, respectively, at 2000 mg/m2. At the tested doses, administration of doranidazole was tolerable and achieved serum concentrations at which reasonable radiosensitization could be expected. A phase Ib/II study to evaluate the feasibility and efficacy of up to 30 repeat administrations seems to be warranted.

Adult↗

Adult onset nocturnal enuresis.

PURPOSE: We determined the etiology and prognostic significance of adult onset enuresis with absent daytime incontinence. Adult onset nocturnal enuresis unassociated with daytime incontinence is uncommon and there is a paucity of information about its incidence, significance, evaluation and treatment. We present a retrospective evaluation of this condition based on a database review of more than 3,000 consecutive patients referred for the evaluation of lower urinary tract symptoms. MATERIALS AND METHODS: A database of 3,277 consecutive patients was searched for adult onset nocturnal enuresis. Patients with daytime incontinence were excluded from study. Evaluation consisted of history, physical examination, American Urological Association symptom score, voiding diary, uroflowmetry, estimation of post-void residual urine, video urodynamics, cystoscopy and radiographic evaluation of the upper tract. RESULTS: Of 3,277 patients 8 (0.02%) had adult onset nocturnal enuresis without daytime incontinence as a primary complaint. Average American Urological Association symptom score was 12.6 (range 3 to 25), average maximum urine flow was 8.5 ml. per second (range 5 to 15) and average post-void residual urine volume was 350 ml. (range 50 to 489). All patients were men with severe prostatic or vesical neck obstruction as well as bilateral or unilateral hydronephrosis in 63%, a bladder diverticulum in 38%, vesicoureteral reflux in 50% and low bladder compliance in 50%. Transurethral prostatic resection was recommended to all patients but only 5 agreed. The other 3 cases were managed by alpha-adrenergic antagonists, including 2 by adjunctive clean intermittent self-catheterization. In all patients who underwent transurethral prostatic resection symptoms resolved, as did hydronephrosis when present. CONCLUSIONS: Adult onset nocturnal enuresis with absent daytime incontinence is a serious symptom that usually heralds significant urethral obstruction, and a high incidence of bladder diverticulum, hydronephrosis and vesicoureteral reflux. It demands urological investigation and aggressive therapy.

Age of Onset↗

Effect of elbow joint angle on the magnitude of muscle damage to the elbow flexors.

PURPOSE: It has been shown that eccentric actions at a long muscle length result in a larger decrease in force and more muscle tenderness compared with those at a short muscle length. To further investigate the effect of elbow joint angle on the development of muscle damage, this study compared two maximal eccentric exercise regimens in which the starting position of the action was different, but the range of movement was the same. METHODS: One arm of 10 male students performed 24 maximal eccentric actions of the elbow flexors at the elbow joint angle from 0.87 to 2.27 rad (50-130 degrees: S condition) and the other arm at the elbow joint angle from 1.74 to 3.14 rad (100-180 degrees: L condition). Maximal isometric force, range of motion, muscle soreness, plasma creatine kinase activity, upper arm circumference, and B-mode ultrasound pictures of the elbow flexors (US) were measured before and for 5 d postexercise in both conditions. Magnetic resonance imaging (MRI) of the transverse scans of the upper arm was taken at 4 d after exercise. RESULTS: All measures changed significantly (P < 0.01) after exercise for both conditions; however, significantly (P < 0.01) larger changes in the measures were found in the L condition compared with the S condition. MRI and US displayed that only the brachialis was damaged for the S condition but the biceps brachii was also damaged for the L condition. CONCLUSION: The greater development of muscle damage in the L condition compared with the S condition is likely to be associated with the elbow flexors muscles affected by the exercise.

Adult↗

How long does the protective effect on eccentric exercise-induced muscle damage last?

PURPOSE: One bout of eccentric exercise produces an adaptation that reduces muscle damage in subsequent bouts. Because it is not known how long this adaptation lasts, the present study investigated the maximal length of the attenuated changes in muscle damage indicators after high-force eccentric exercise. METHODS: Male students (N = 35) were placed into three groups and performed two bouts of eccentric exercise of the nondominant elbow flexors separated by either 6 (N = 14), 9 (N = 11), or 12 (N = 10) months. Maximal isometric force (MIF), range of motion (ROM), upper arm circumference (CIR), muscle soreness (SOR), and plasma creatine kinase activity (CK) were measured before and for 5 d after exercise. Magnetic resonance (MR) images of the transverse and longitudinal scans of the upper arm were taken 4 d after exercise. Changes in the criterion measures were compared between the first and second bouts and between groups by a two-way repeated measures ANOVA. RESULTS: A faster recovery in MIF was evident after a second bout performed at 6 or 9 months, and reduced SOR as well as smaller increases in CIR, CK, and T2 relaxation time of MR images also occurred after the second exercise bout at 6 months compared with initial responses. No significant differences between the bouts were found for ROM, and the 12-month group did not show any repeated bout effect. CONCLUSION: These results show that the repeated bout effect for most of the criterion measures lasts at least 6 months but is lost between 9 and 12 months.

Adolescent↗

Hop resistance in the beer spoilage bacterium Lactobacillus brevis is mediated by the ATP-binding cassette multidrug transporter HorA.

Lactobacillus brevis is a major contaminant of spoiled beer. The organism can grow in beer in spite of the presence of antibacterial hop compounds that give the beer a bitter taste. The hop resistance in L. brevis is, at least in part, dependent on the expression of the horA gene. The deduced amino acid sequence of HorA is 53% identical to that of LmrA, an ATP-binding cassette multidrug transporter in Lactococcus lactis. To study the role of HorA in hop resistance, HorA was functionally expressed in L. lactis as a hexa-histidine-tagged protein using the nisin-controlled gene expression system. HorA expression increased the resistance of L. lactis to hop compounds and cytotoxic drugs. Drug transport studies with L. lactis cells and membrane vesicles and with proteoliposomes containing purified HorA protein identified HorA as a new member of the ABC family of multidrug transporters.

ATP-Binding Cassette Transporters↗

Static stretch increases c-Jun NH2-terminal kinase activity and p38 phosphorylation in rat skeletal muscle.

Physical exercise and contraction increase c-Jun NH2-terminal kinase (JNK) activity in rat and human skeletal muscle, and eccentric contractions activate JNK to a greater extent than concentric contractions in human skeletal muscle. Because eccentric contractions include a lengthening or stretch component, we compared the effects of isometric contraction and static stretch on JNK and p38, the stress-activated protein kinases. Soleus and extensor digitorum longus (EDL) muscles dissected from 50- to 90-g male Sprague-Dawley rats were subjected to 10 min of electrical stimulation that produced contractions and/or to 10 min of stretch (0.24 N tension, 20-25% increase in length) in vitro. In the soleus muscle, contraction resulted in a small, but significant, increase in JNK activity (1.8-fold above basal) and p38 phosphorylation (4-fold). Static stretch had a much more profound effect on the stress-activated protein kinases, increasing JNK activity 19-fold and p38 phosphorylation 21-fold. Increases in JNK activation and p38 phosphorylation in response to static stretch were fiber-type dependent, with greater increases occurring in the soleus than in the EDL. Immunohistochemistry performed with a phosphospecific antibody revealed that activation of JNK occurred within the muscle fibers. These studies suggest that the stretch component of a muscle contraction may be a major contributor to the increases in JNK activity and p38 phosphorylation observed after exercise in vivo.

Animals↗

Effects of amino acid substitution on the physicochemical properties of artificial proteins with random sequences.

Physicochemical properties of four random proteins, each consisting of about 150 amino acid residues with different sequence identity, were compared to know the correlation between the physicochemical properties and its sequence. The results showed that the extent of the sequence alterations correlated well with the extent of differences in CD spectra, roughly with those in pH-solubility profiles and sedimentation velocity, and not with that in the binding of a hydrophobic fluorescent dye (ANS). Therefore, proteins with similar sequences can have different physicochemical properties, indicating that the extent of mutational effects varies in response to the sequence being altered. This warrants the evolution of a protein in a sequence-specific manner.

Journal Article↗

Open-wedge osteotomy of the proximal tibia with hemicallotasis.

Conventional high tibial osteotomy for losteoarthritis of the medial compartment of the knee with closed-wedge or dome osteotomy (DMO) may produce shortening of the patellar tendon and loss of inclination of the proximal tibial plateau or of the offset of the tibial condyle relative to its bony axis. This can make subsequent total knee arthroplasty technically demanding. We undertook a prospective study comparing these changes after DMO with those after using open-wedge osteotomy hemicallotasis (HCO). A total of 50 knees with arthritis of the medial compartment in 46 consecutive patients was randomly allocated to either DMO or HCO. There were no significant differences between the groups with regard to age, gender, femorotibial angle before operation or the angle of correction. Radiological studies showed that HCO caused little change in the length of the patellar tendon or the inclination angle of the tibial plateau, while after DMO both gradually decreased. The degree of tibial condylar offset increased in both groups, but less so in the HCO group.

Aged↗

Eradication of foot and mouth disease in Japan.

An outbreak of foot and mouth disease (FMD) was recorded in Japan in the spring of 2000, the first for ninety-two years. Between 25 March and 11 May, four farms were infected. However, the disease was eradicated without resorting to vaccination, through a campaign of culling, movement control of cloven-hoofed animals in areas surrounding infected premises, and intensive clinical and serological surveillance. Japan regained FMD-free status by the end of September 2000. The authors describe the nature of the outbreaks, the eradication measures implemented, and the clinical and serological surveillance methods used. The possible sources of infection are also examined. Finally, the direct and indirect economic losses are presented.

Animals↗

Spontaneous blinks as a criterion of visual fatigue during prolonged work on visual display terminals.

Visual fatigue caused by prolonged work viewing a Visual Display Terminals (VDT) and of work reading a hard-copy were assessed by electromyogram (EMG) waveform and electrooculogram (EOG) waveform in spontaneous blinks as objective criteria, and by questionnaire of subjective feeling, and by task performance. The duration and the amplitude of the EMG of the orbicularis ocular muscle on the right side and the EOG of the vertical direction to the eyelid were measured for 10 subjects who participated in a figure task consisting of the addition of single-digit numbers on a VDT work or a work with a hard-copy. The mean values of the duration and the amplitude of the EMG and the EOG were evaluated by the averaging of 10 waveforms of the spontaneous blinks for all subjects. The time lag from the EMG to the EOG in the process of the generation of spontaneous blinks was also analyzed. These five parameters were evaluated during the work time. The mean values for the duration of the EMG increased gradually during the work time, but the amplitude did not show significant difference between the prework and a work time. There was no significant change of the duration of the EOG, but the mean amplitude of the EOG decreased as the work time progressed, and the time lag significantly extended. The blinks frequency increased relatively when using a VDT. The rate of fluctuation for these parameters was higher during use of a VDT than use of a hard-copy. The time lag at five hours of VDT work was extended by 90% based on the value at the pre-work. The symptoms of general fatigue and fatigue of the eyes increased linearly during the VDT work for six hours. The results indicated a significant correlation between the objective parameters for the activity of the spontaneous blinks, i.e., duration and amplitude of EMG and EOG, and the time lag between EMG and EOG, and the subjective feeling was recognized in the time course of the task. These experimental results suggested that the parameters regarding the EMG and the EOG for the spontaneous blinks were effective indices for assessing visual fatigue during prolonged VDT work.

Adult↗

FR198248, a new anti-influenza agent isolated from Apsergillus terreus No 13830. I. Taxomony, fermentation, isolation, physico-chemical properties and biological activities.

A novel anti-influenza agent, FR198248, was isolated from the cultured broth of a fungal strain No.13830. The strain was identified as Aspergillus terreus from morphological characteristics. FR198248, a new type of hydroxyl benzaldehyde compound, showed antiinfluenza virus activity in Madin-Darby canine kidney (MDCK) cells in vitro. The mode of action of FR198248 against influenza virus A could be ascribed to an inhibitory effect on the stage of virus adsorption. Furthermore, FR198248 possessed potent in vivo anti-influenza activity in a murine model of respiratory tract infection.

Animals↗

Sensory disturbance of the thigh after renal transplantation.

PURPOSE: Although sensory disturbance of the anterior and/or lateral thigh often develops after renal transplantation, this complication is overlooked because of the minor degree of disability. We evaluated the rate of sensory disturbance of the thigh after renal transplantation. MATERIALS AND METHODS: We examined neurological deficits of the thigh on the operated side in 61 patients who underwent renal transplantation, including 48 using the internal and 13 using the external iliac artery. RESULTS: We noted sensory disturbance in 23 of the 61 cases, including 20 of the 48 in which the internal iliac artery was used. One patient had complete femoral nerve palsy involving motor weakness. Sensory disturbance was in the anterior thigh in 15 patients, in the lateral thigh in 3, and on the anterior and lateral thigh in 2. Postoperatively there was sensory disturbance of the thigh in 3 of the 13 patients in whom the external iliac artery was used. Sensory disturbance persists in all 3 cases at the time of this report, including in the anterior thigh in 1, and in the anterior and lateral thigh in 2. CONCLUSIONS: The rate of sensory disturbance of the thigh after renal transplantation is high. Therefore, we should inform patients of the possibility of sensory disturbance before renal transplantation surgery is performed.

Femoral Nerve↗

IL-6 and IFN-gamma regulation of IL-10 production by human colon carcinoma cells.

IL-10 has been shown to play a crucial role in immunosuppression in cancer patients. We explored the regulation of IL-10 production by TNF-alpha, IL-1 beta, IL-6, IL-8, and IFN-gamma in human colon carcinoma COLO205 cells. Northern analysis revealed a marked expression of IL-10 mRNA after stimulation by IL-6, and a marginal but significant expression by TNF-alpha, IL-1 beta or IFN-gamma. No IL-10 mRNA expression was observed when cells were untreated or incubated with IL-8. IL-10 in the culture supernatants showed good agreement with mRNA expression. In addition, IFN-gamma dose-dependently inhibited this IL-6-induced production of IL-10. MTT assay revealed that low dose IFN-gamma (1-10 ng/ml) had no effect on growth of COLO205 cells, but that high dose IFN-gamma (>100 ng/ml) significantly inhibited their proliferation. Northern analysis of COLO205 cells pretreated with IFN-gamma demonstrated that the IL-6R alpha chain was down-regulated. These results suggest that, in certain colon carcinoma cells, tumor-derived IL-10 production is directly regulated by systemic or local production of pro-inflammatory cytokines, such as IL-6 and IFN-gamma.

Blotting, Northern↗

[Desmoid tumor of the chest wall infiltrating into the brachial plexus: report of a resected case].

We report a case of a desmoid tumor which developed in the apex of the chest wall. A 18-year-old woman was admitted with left shoulder pain. Chest X-ray showed a mass shadow in the left upper lung field. Chest MRI demonstrated the mass infiltrated into the left brachial plexus. A desmoid tumor was suspected on percutaneous needle biopsy. Resection of the tumor was performed. The mass was 13 x 9 x 5 cm in size and diagnosed pathologically as desmoid tumor. Adjunctive postoperative radiation therapy of 60 Gy was done. Postoperative course was uneventful except motor disturbances of the left fingers. At 15 months postoperatively, there was no evidence of recurrence.

Adolescent↗

Spontaneous blinks of Parkinson's disease patients evaluated by EMG and EOG.

In a study of spontaneous blinks, both electromyographic (EMG) activities from m. orbicularis oculi which is responsible for initiating closure of the eyelid and electro-oculogram (EOG) of vertical direction to the movement of the eyelid were measured in ten patients with Parkinson's disease and in thirty normal subjects. The aim of this study was to evaluate the generative mechanism of the spontaneous blinks by comparison of both the EMG and the EOG waveforms in the patients with Parkinson's disease and those in the normal subjects. The mean duration and the amplitude of both the EMG and the EOG were evaluated by the averaging of ten waveforms for the spontaneous blinks. The time lag between the onset of the generation of the EMG and the onset of the EOG signal was analyzed. The mean duration of the EMG and the mean amplitude of both the EMG and the EOG in the patients with Parkinson's disease were shorter and smaller than those in the normal subjects by the significant level of 1%, respectively. There was no difference of the time lag between the subject groups. These results suggest that the function of m. orbicularis oculi for the spontaneous blinks is reduced in patients with Parkinson's disease, because the motoneurones of the facial nucleus innervating the m. orbicularis oculi becomes hypoactive due to abnormal output of basal ganglia.

Aged↗