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Biomedical subjects

M Ishikawa

Publications and source records attributed to M Ishikawa.

At least 19 recordsLinked to original sources

Intensity- and muscle-specific fascicle behavior during human drop jumps.

The present study was designed to examine fascicle-tendon interaction in the synergistic medial gastrocnemius (MG) and soleus (Sol) muscles during drop jumps (DJ) performed from different drop heights (DH). Eight subjects performed unilateral DJ with maximal rebounds on a sledge apparatus from different DH. During the exercises, fascicle lengths (using ultrasonography) and electromyographic activities were recorded. The results showed that the fascicles of the MG and Sol muscles behaved differently during the contact phase, but the whole muscle-tendon unit and its tendinous tissue lengthened before shortening in both muscles. The Sol fascicles also lengthened before shortening during the ground contact in all conditions. During the braking phase, the Sol activation increased with increasing DH. However, the amplitude of Sol fascicle lengthening was not dependent on DH during the same phase. In the MG muscle, the fascicles primarily shortened during the braking phase in the lower DH condition. However, in the higher DH conditions, the MG fascicles either behaved isometrically or were lengthened during the braking phase. These results suggest that the fascicles of synergistic muscles (MG and Sol) can behave differently during DJ and that, with increasing DH, there may be specific length change patterns of the fascicles of MG but not of Sol.

Adult↗

Medial gastrocnemius muscle behavior during human running and walking.

Utilization of elastic energy in the tendinous tissues (TT) of the human skeletal muscle may be task dependent. The present study was designed to investigate this problem by comparing the fascicle-TT interaction of the medial gastrocnemius muscle (MG) during ground contact of running and walking. Seven subjects ran and walked with a natural cadence. Ankle and knee joint angular data were recorded by electrogoniometers for estimating the entire MG muscle-tendon unit (MTU) length, together with the ground reaction forces. The MG fascicle length was measured by using the high-speed ultrasound image scanning during movements. The results showed that in running, after the rapid early fascicle stretching (0-10% of the contact period), the fascicles shortened throughout the ground contact while TT was stretched prior to shortening. In walking, the fascicles shortened initially (0-15% of the contact period) due to sudden plantar-flexion. Thereafter, the fascicles and TT lengthened slowly until the end of single support (15-70% of the contact period.). The fascicles then shorted during the push-off phase (70-100% of the contact period). These results demonstrate that the MG fascicles behaved differently between running and walking and did not follow the length change pattern of the MTU during the ground contact period. The estimated working range of active muscle fibers in force-length relationship could shift more to an ascending limb (shorter length) phase in running than in walking. These results suggest that MG fascicles can work within the optimal working range of the sarcomeres in the force-length relation but are responsible for the effective utilization of the TT elasticity during human running.

Adult↗

Prostate cancer incidence varies among males from different Y-chromosome lineages.

The incidence rate of prostate cancer in African-American males is two times higher than Caucasian men and ten times higher than Japanese men. The geographical specificity of Y haplogroups implies that males from different ethnic groups undoubtedly have various Y lineages with different Y-chromosomal characteristics that may affect their susceptibility or resistance to such a male-specific cancer. To confirm this hypothesis we studied the Y-chromosomal haplogroups of 92 Japanese prostate cancer patients comparing them with randomly selected 109 unrelated healthy Japanese male controls who were confirmed to be residents of the same geographical area. Males could be classified using three binary Y-chromosome markers (sex-determining region Y (SRY), YAP, 47z) into four haplogroups DE, O2b(*), O2b1, and untagged group. Our results confirmed that prostate cancer incidence varies among males from different Y-chromosome lineages. Males from DE and the untagged haplogroups are at a significantly higher risk to develop prostate cancer than O2b(*) and O2b1 haplogroups (P=0.01), odds ratio 2.17 and 95% confidence interval (1.16-4.07). Males from haplogroup DE are over-represented in the patient group showing a percentage of 41.3%. The underlying possible causes of susceptibility variations of different Y lineages for such a male-specific cancer tumorigenesis are discussed. These findings explain the lower incidence of prostate cancer in Japanese and other South East Asian males than other populations. To our knowledge, this is the first reliable study examining the association between prostate cancer and Y-chromosomal haplogroups, comparing prostate cancer patients with carefully selected matched controls.

Carcinoma↗

Changes in the soleus muscle architecture after exhausting stretch-shortening cycle exercise in humans.

This study focused on the architectural changes in the muscle-tendon complex during the immediate and secondary (delayed) reductions of performance (bimodal recovery) caused by an exhaustive rebound type stretch-shortening cycle (SSC) exercise. The isometric plantar flexor torque during maximum voluntary contraction (MVC) was measured together with recording of electromyography (EMG) and ultrasonography from the soleus muscle before (BEF), after (AFT), 2 h (2H), 2 and 8 days (2D, 8D) after the SSC exercise (n=8). The performance variables (MVC torque and EMG activation) followed the bimodal recovery patterns. This was not the case in the changes of the fascicle length and muscle thickness. The relative torque changes in MVC correlated positively (R=0.78, P=0.02) to the corresponding averaged EMG changes between BEF and 2H (BEF-->2H); the significance disappeared in the comparison between 2H and 2D (2H-->2D), during which period MVC showed a secondary reduction. The relative torque changes in MVC showed no correlation with the changes in muscle thickness between BEF-2H. However, this correlation between 2H-2D was negative (R=-0.85, P<0.01). The fascicle shortening/average EMG ratio in MVC increased at 2H, and then decreased more at 2D than 2H (P<0.05). Thus, the secondary performance decline was not related to the corresponding EMG reduction but to the increased muscle thickness, which peaked at 2D. The results suggest clearly that the secondary decline in MVC could be related to the increase in muscle volume.

Adult↗

Involvement of brain protein kinase C in nitrous oxide-induced antinociception in mice.

Exposure of mice to the anesthetic gas nitrous oxide (N(2)O) produces a marked antinociceptive effect. Protein kinase C is a key regulatory enzyme that may be targeted by general anesthetics. However, a relationship between N(2)O-induced antinociception and protein kinase C has yet to be established. The present study was conducted to identify whether protein kinase C might influence N(2)O-induced antinociception in mice. Regular exposure (11 min) to N(2)O produced concentration-dependent antinociception in mice, as determined using the abdominal constriction test. N(2)O-induced antinociception was attenuated by i.c.v. pretreatment with phorbol 12,13-dibutyrate, a protein kinase C activator. This phorbol 12,13-dibutyrate antagonism of N(2)O-induced antinociception was reversed by i.c.v. pretreatment with calphostin C, a protein kinase C inhibitor. Long-term exposure (41 min in total, including 30 min prior to, and 11 min of analgesic testing) to 70% N(2)O produced reduced analgesic effects, compared with regular exposure to 70% N(2)O, thus indicating acute tolerance to N(2)O-induced antinociception. However, mice pretreated with calphostin C, chelerythrine, which is another protein kinase C inhibitor, and phorbol 12,13-dibutyrate, did not develop acute tolerance. Regarding activation of protein kinase C, regular exposure to 70% N(2)O did not increase protein kinase C within the membrane fraction of brain tissue, as determined by immunoblot analysis, but long-term exposure to 70% N(2)O did. The i.c.v. pretreatment with calphostin C and phorbol 12,13-dibutyrate prevented the increase in protein kinase C observed with long-term exposure to 70% N(2)O. These results suggest that brain protein kinase C negatively regulates the antinociceptive effect of N(2)O, and that activation of brain protein kinase C is related to the development of acute tolerance to N(2)O-induced antinociception in mice.

Analgesics↗

Inducible virus-mediated expression of a foreign protein in suspension-cultured plant cells.

Although suspension-cultured plant cells have many potential merits as sources of useful proteins, the lack of an efficient expression system has prevented using this approach. In this study, we established an inducible tomato mosaic virus (ToMV) infection system in tobacco BY-2 suspension-cultured cells to inducibly and efficiently produce a foreign protein. In this system, a modified ToMV encoding a foreign protein as replacement of the coat protein is expressed from stably transformed cDNA under the control of an estrogen-inducible promoter in transgenic BY-2 cells. Estrogen added to the culture activates an estrogen-inducible transactivator expressed constitutively from the transgene and induces transcription and replication of viral RNA. In our experiments, accumulation of viral RNA and expression of green fluorescent protein (GFP) encoded in the virus were observed within 24 h after induction. The amount of GFP reached approximately 10% of total soluble protein 4 d after induction. In contrast, neither viral RNA nor GFP were detected in uninduced cells. The inducible virus infection system established here should be utilized not only for the expression of foreign proteins, but also for investigations into the viral replication process in cultured plant cells.

Capsid Proteins↗

Prevalence and risk factor analysis of microalbuminuria in Japanese general population: the Takahata study.

Microalbuminuria, an indicator of glomerular injury, is associated with increased risk of progressive renal deterioration, cardiovascular disease, and mortality. However, the prevalence of microalbuminuria in Japanese general population is less certain. Thus, we examined the prevalence of microalbuminuria and its associated risk factors in Japan. Subjects of this cross-sectional study were asymptomatic individuals over 40 years in Takahata, Japan. Urine albumin-creatinine ratio was calculated from a single-spot urine specimen collected in the morning. Creatinine clearance (CCr) was obtained by Cockcroft-Gault equation. Multivariate logistic regression analysis was used to determine which risk factors (i.e., age, hypertension, diabetes, obesity, and salt intake) might predict the presence of microalbuminuria. A total of 2321 subjects (mean age, 64 years; men, 1034; women, 1287) were entered into the final analysis. Among them, the prevalence of microalbuminuria, macroalbuminuria, and proteinuria by dipstick test (> or = 1+) were 317 (13.7%), 39 (1.7%), and 103 (4.4%), respectively. Age, hypertension, and diabetes were independently associated with microalbuminuria in men. In addition to the classical risk factors detected in men, estimated 24-h urinary sodium excretion and uric acid were also independently associated with microalbuminuria in women. Among the 668 subjects with renal insufficiency (CCr <60 ml/min/1.73 m(2)), the prevalence of microalbuminuria and macroalbuminuria were 119 (17.8%) and 18 (2.7%), respectively. In conclusion, microalbuminuria is prevalent across all age groups and is associated with lifestyle-related risk factors in Japanese general population. However, there are a substantial number of subjects with renal insufficiency accompanying no microalbuminuria.

Aged↗

Lead isotope ratios in urban road runoff.

Lead isotopic analyses of road runoff and airborne particulate matter have been carried out to elucidate sources of lead pollution at urban and suburban sites. While lead is often observed in road runoff in suspended form, suspended particle size had no relation to the lead isotopic distribution, as a result of comparison between runoff samples with total suspended solids and those with minute particles passed through a 75 microm sieve. Lead isotope ratios in airborne particulate matter in urban areas fell within a wider range than those in road runoff. Since there was little difference of the ratios between a heavy traffic-flow site and residential sites, airborne lead derived from vehicle exhaust was found to make little contribution to the contamination of road runoff. On the other hand, the ratios in road runoff at a suburban site showed the same range as those at an urban site. Lead in road runoff was therefore suggested to be produced on site by traffic related substances, such as tire wear, other than vehicle exhaust.

Air Pollutants↗

Influence of ABCB1 C3435T polymorphism on the pharmacokinetics of lansoprazole and gastroesophageal symptoms in Japanese renal transplant recipients classified as CYP2C19 extensive metabolizers and treated with tacrolimus.

OBJECTIVE: Lansoprazole and tacrolimus are substrates of ATP binding cassette (ABC) transporters such as P-glycoprotein (ABCBI/multidrug resistance 1) and cytochrome P450 (CYP). The purpose of this study was to investigate the implication of the ABCB1 C3435Tpolymorphism on the pharmacokinetics of (R)-lansoprazole, the major enantiomer, in CYP2C19 extensive metabolizers (EMs) and on gastroesophageal symptoms in renal transplant recipients receiving tacrolimus. MATERIALS: 24 recipients who were CYP2C19 EMs were studied. METHODS: Oral administration of 30 mg lansoprazole was started 2 days before transplantation. On Day 2 before and Day 28 after transplantation, the plasma concentrations of (R)-lansoprazole and tacrolimus were measured. RESULTS: Pretransplantation, there were no significant differences in the pharmacokinetic parameters of (R)-lansoprazole between the 3 ABCBI C3435T genotypes. However, after renal transplantation, the peak plasma concentration (Cma ) and area under the plasma concentration-time curve (AUCO-24) of (R)-lansoprazole in patients with the ABCB1 C3435T C allele significantly increased, but not in patients with the TT genotype. These pharmacokinetic variations in (R)-lansoprazole did not influence the AUC of tacrolimus. There were no significant differences in the frequency of gastroesophageal symptoms among the three ABCB] C3435Tgenotypes. CONCLUSIONS: (R)-lansoprazole concentrations significantly increased in CYP2C19 extensive metabolizers with the ABCB1 C3435T C allele, but not TT genotype, after renal transplantation. However, the clinical relevance of this observation may be minor because these pharmacogenetic changes were not associated with the occurrence of gastroesophageal complications.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Successive changes in tissue migration capacity of developing larvae of an intestinal nematode, Strongyloides venezuelensis.

Infective larvae of an intestinal nematode, Strongyloides venezuelensis, enter rodent hosts percutaneously, and migrate through connective tissues and lungs. Then they arrive at the small intestine, where they reach maturity. It is not known how S. venezuelensis larvae develop during tissue migration. Here we demonstrate that tissue invasion ability of S. venezuelensis larvae changes drastically during tissue migration, and that the changes are associated with stage-specific protein expression. Infective larvae, connective tissue larvae, lung larvae, and mucosal larvae were used to infect mice by various infection methods, including percutaneous, subcutaneous, oral, and intraduodenal inoculation. Among different migration stages, only infective larvae penetrated mouse skin. Larvae, once inside the host, quickly lost skin penetration ability, which was associated with the disappearance of an infective larva-specific metalloprotease. Migrating larvae had connective tissue migration ability until in the lungs, where larvae became able to settle down in the intestinal mucosa. Lung larvae and mucosal larvae were capable of producing and secreting adhesion molecules.

Animals↗

Interaction between fascicle and tendinous tissues in short-contact stretch-shortening cycle exercise with varying eccentric intensities.

The interaction between fascicle and tendinous tissues (TT) in short-contact drop jumps (DJ) with three different drop heights [low (Low), optimal (OP), and high (High)] was examined with 11 subjects. The ground reaction force (F(z)) and ankle and knee joint angles were measured together with real-time ultrasonography (fascicle length) and electromyographic activities of the medial gastrocnemius (MG) and vastus lateralis (VL) muscles during the movement. With increasing drop height, the braking force and flight time increased from Low to OP (P < 0.05). In High, the braking force increased but the flight time decreased compared with OP (P < 0.05). During contact of Low and OP conditions, the length of muscle-tendon unit and TT underwent lengthening before shortening in both MG and VL muscles. However, the two muscles differed in the fascicle behaviors. The MG fascicles behaved isometrically or shortened, and the VL fascicles underwent lengthening before shortening during contact. In High, the TT lengthening in both muscles decreased compared with OP (P < 0.05). The rapid stretch occurred in the MG fascicles but not in VL fascicles during the braking phase. The elastic recoil ratio decreased in both muscles with increasing the intensity during DJ. These findings demonstrated that TT underwent lengthening before shortening during DJ. However, the efficacy of elastic recoil decreased with increasing the drop intensity. The effective catapult action in TT can be limited by the drop intensity. In addition, the measured muscles behaved differently during DJ, providing evidence that each muscle may have a specific means of fascicle-TT interaction.

Adult↗

Replica multichannel polymer chips with a network of sacrificial channels sealed by adhesive printing method.

Replica microchips for capillary array electrophoresis containing 10 separation channels (50 microm width, 50 microm depth and 100 microm pitch) and a network of sacrificial channels (100 microm width and 50 microm depth) were successfully fabricated on a poly(methyl methacrylate) (PMMA) substrate by injection molding. The strategy involved development of moving mask deep X-ray lithography to fabricate an array of channels with inclined channel sidewalls. A slight inclination of channel sidewalls, which can not be fabricated by conventional deep X-ray lithography, is highly required to ensure the release of replicated polymer chips from a mold. Moreover, the sealing of molded PMMA multichannel chips with a PMMA cover film was achieved by a novel bonding technique involving adhesive printing and a network of sacrificial channels. An adhesive printing process enables us to precisely control the thickness of an adhesive layer, and a network of sacrificial channels makes it possible to remove air bubbles and an excess adhesive, which are crucial to achieving perfect sealing of replica PMMA chips with well-defined channel and injection structures. A CCD camera equipped with an image intensifier was used to simultaneously monitor electrophoretic separations in ten micro-channels with laser-induced fluorescence detection. High-speed and high-throughput separations of a 100 bp DNA ladder and phi X174 Hae III DNA restriction fragments have been demonstrated using a 10-channel PMMA chip. The current work establishes the feasibility of mass production of PMMA multichannel chips at a cost-effective basis.

Adhesives↗

A stylized computational model of the head for the reference Japanese male.

Computational models of human anatomy, along with Monte Carlo radiation transport simulations, have been used by Snyder et al. [MIRD Pamphlet No. 5, revised (The Society of Nuclear Medicine, New York, 1978)], Cristy and Eckerman [ORNL/TM-8381/VI, Oak Ridge National Laboratory, Oak Ridge, TN (1987)] and Zubal et al. [Med. Phys. 21, 299-302 (1994)] to estimate internal organ doses from internal and external radiation sources. These were created using physiological data from Caucasoid subjects but not from other races. There is a need for research to determine whether the obvious differences from the Caucasoid anatomy make these models unsuitable for estimating the absorbed dose in other races such as the Mongoloid. We used the cranial region of the adult Japanese male to represent the Mongoloid race. This region contains organs that are highly sensitive to radiation. The cranial region of a physical phantom produced by KYOTO KAGAKU Co., LTD. using numerical data from a Japanese Reference Man [Tanaka, Nippon Acta. Radiol. 48, 509-513 (1988)] was used to supply the data for the geometry of a stylized computational model. Our computational model was constructed with equations rather than voxel-based, in order to deal with as small a number of parameters as possible in the computer simulation experiment. The accuracy of our computational model was checked by comparing simulated experimental results obtained with MCNP4C with actual doses measured with thermoluminescence dosimeters (TLDs) inside the physical phantom from which our computational model was constructed. The TLDs, whose margin of error is less than +/-10%, were arranged at six positions. Co-60 was used as the radiation source. The irradiated dose was 2 Gy in terms of air kerma. In the computer simulation experiments, we used our computational model and Cristy's computational model, whose component data are those of the tissue substitute materials and of the human body as published in ICRU Report 46. The observed absorbed dose values (Gy) at all six points were calculated as the percentage difference between MCNP4C simulation and the TLDs. In our computational model, the average values of all the percentage differences were 6.0+/-4.0% (tissue substitute materials) and 7.6+/-6.6% (ICRU Report 46), respectively. In Cristy's model, the corresponding values were 20.4+/-3.8% (tissue substitute materials) and 21.0+/-4.1% (ICRU Report 46), respectively. Considering the margin of error in the radiation sensitivity of the TLDs, this study validates our computational model as a test object for radiation dosimetry studies.

Asian People↗

[Traumatic rupture of the ascending aorta].

A 42-year-old male was diagnosed as having a traumatic rupture of the ascending aorta 24 hours after traffic accident. On admission, the patient was in a state of shock, but he was successfully treated by emergency surgery. Traumatic rupture of the ascending aorta is a serious condition and the mortality may be very high. Although physicians rarely encounter patients with this condition, it is relatively common among autopsy cases with multiple trauma. Urgent diagnosis and treatment are mandatory.

Adult↗

A pilot study of weekly docetaxel therapy for recurrent ovarian cancer, tubal cancer, and primary peritoneal cancer.

We investigated the efficacy and toxicity of salvage chemotherapy with weekly docetaxel for recurrent ovarian cancer, tubal cancer, and primary peritoneal cancer after treatment with regimens containing platinum or paclitaxel. The 15 subjects were managed as outpatients and received at least two courses of docetaxel therapy (35 mg/m2 on days 1, 8 and 15). Antitumour activity was assessed radiologically and from the CA-125 level. Among five patients with measurable lesions, one showed partial remission and three showed stable disease. Based on CA-125 levels, there were three partial remissions and five patients with stable disease (progression-free survival was 7.5 months and 7.6 months, respectively). During 61 courses, the severe toxicities were grade 3 leukopaenia/neutropaenia (6.7%) or grade 2 oedema and pleural effusion (13.3%). Weekly docetaxel may be useful salvage chemotherapy for recurrent ovarian cancer, tubal cancer, and peritoneal cancer, especially as tumour dormancy therapy.

Adult↗

Microarray analysis of brassinosteroids- and gibberellin-regulated gene expression in rice seedlings.

In order to understand the molecular mechanisms by which two types of phytohormones, brassinosteroids (BRs) and gibberellins (GAs), regulate plant growth and development, a cDNA microarray was made containing 4000 clones randomly selected from a rice cDNA library constructed from RNA isolated from seedlings treated with GA(3) and brassinolide (BL). The array was then probed to identify differences in expression using labelled cDNAs prepared from treated and control seedlings. Nine and 29 unique cDNA clones were up-regulated, while 32 and 42 unique cDNA clones were down-regulated by BL and GA(3), respectively. The predicted products of these BL- and GA-regulated genes fall into such functional categories as signal transduction, transcription, metabolism, cellular organization, and defense or anti-stress responses. Northern analysis of the selected BL- and GA(3)-regulated genes not only confirmed their BL or GA(3) dose dependent expression, but also revealed significant differences in the degree of expression in different organs and in response to other phytohormones. These results demonstrate that BR and GA influence growth and development by coordinately regulating the expression of specific groups of genes.

Brassinosteroids↗

Development of real-time thermal neutron monitor using boron-loaded plastic scintillator with optical fiber for boron neutron capture therapy.

A new thermal neutron monitor for boron neutron capture therapy was developed in this study. We called this monitor equipped boron-loaded plastic scintillator that uses optical fiber for signal transmission as an [scintillator with optical fiber] SOF detector. A water phantom experiment was performed to verify how the SOF detector compared with conventional method of measuring thermal neutron fluence. Measurements with a single SOF detector yielded indistinguishable signals for thermal neutrons and gamma rays. To account for the gamma ray contribution in the signal recorded by the SOF detector, a paired SOF detector system was employed. This was composed of an SOF detector with boron-loaded scintillator and an SOF detector with a boron-free scintillator. The difference between the recorded counts of these paired SOF detectors was used as the measure of the gamma ray contribution in the measured neutron fluence. The paired SOF detectors were ascertained to be effective in measuring thermal neutron flux in the range above 10(6)(n/cm(2)/s). Clinical trials using paired SOF to measure thermal neutron flux during therapy confirmed that paired SOF detectors were effective as a real-time thermal neutron flux monitor.

Boron Neutron Capture Therapy↗