PubMed Health⌕ Search

Biomedical subjects

J Kimura

Publications and source records attributed to J Kimura.

At least 19 recordsLinked to original sources

Immunolocalization of gastrin-releasing peptide (GRP) in the uteroplacenta of the mouse deer.

The considerable phylogenetical differences between mouse deer and other ruminants have been established by means of DNA sequence analysis and anatomical observations. To clarify the physiological role of the uteroplacenta of the mouse deer, immunohistochemical observation was attempted by using GRP, which has been suggested as a novel regulatory peptide in the female reproductive tract, as an indicator to compare with other ruminants. Strong positive reactions for the GRP were detected in the uterine glands of the pregnant animals, but not in the non-pregnant ones. Although the placenta of the mouse deer is categorized as a diffuse placenta that is different from other ruminants' polycotyledonary placenta, in terms of GRP immunoreactivity, the mouse deer placenta can be classified as a synepithecholial placenta like the other ruminants'. The secretion of GRP from the uterine glands is of some importance to the fetus in the mouse deer.

Animals↗

Three-dimensional reconstruction of the equine ovary.

The equine ovary has a very unique structure in terms of its extreme large size, the presence of the ovulation fossa and the inverted location of its cortex and medulla. In the previous study, it was recognized that the application of three-dimensional internal structure microscopy (3D-ISM) to observe the mare ovary is very effective. Three-dimensional reconstruction of serially sliced images made by 3D-ISM was successful in this study with the aid of the sophisticated image processing technique. The rotation of the reconstructed ovary has been carried out with and without the application of the transparency technique in the ovarian stromal region. The spatial localization of follicles and corpus luteum was clearly visualized by rotating the reconstructed image of the ovary. The extraction of the images of follicles and corpus luteum was also available and gave a quantifiable understanding of their structure.

Animals↗

An ultrastructural study on the Leydig and Sertoli cells in the immature lesser mouse deer (Tragulus javanicus).

Leydig and Sertoli cells of the immature lesser mouse deer testes, obtained in East Malaysia, were observed using light and transmission electron microscopy (TEM). The testes were fixed in 5% glutaraldehyde, post-fixed in 1% OsO4, dehydrated in ethanol, and embedded in Araldite M. Serial semi-thin sections were cut, stained with toluidine blue and observed using light microscopy. Serial ultra-thin sections were cut, stained with uranyl acetate and lead citrate, and examined using TEM. As a result, ultrastructurally, two types of underdeveloped filament bundles were infrequently recognized in Leydig cells, but not in other testicular cells. One type was the underdeveloped bundles of actin filaments (approximately 5 nm in diameter), which were found in the nucleus of Leydig cells. The other type was the underdeveloped bundles of intermediate filaments (approximately 10 nm in diameter), which were found in the cytoplasm of Leydig cells. A multivesicular nuclear body (MNB)--specifically present in the Sertoli cell nucleus of ruminant testes--was infrequently observed. The MNB is situated in the vicinity of nuclear membrane, still in an underdeveloped stage.

Actins↗

Ectoparasites of the Pallas squirrel, Callosciurus erythraeus, introduced to Japan.

The squirrel Callosciurus erythraeus (Pallas) (Rodentia: Sciuridae) was intentionally introduced to Japan in 1935 and has become established throughout much of the country. Although they live mainly in forests, Pallas squirrels come into gardens and are frequently fed by people or kept as pets, so their ectoparasites could be of potential medical as well as veterinary importance. During 2001-2003 we conducted the first ectoparasite survey of Pallas squirrels in Japan. From 105 C. erythraeus captured in Kamakura District of Kanagawa Prefecture on Honshu Island, three types of ectoparasite were found: 52 specimens of the sucking louse Neohaematopinus callosciuri Johnson (Anoplura: Haematopinidae), 26 fleas Ceratophyllus (Monopsyllus) anisus Rothschild (Siphonaptera: Ceratophyllidae) and four nymphs of the tick Haemaphysalis flava Neumann (Acari: Ixodidae) on 22, 13 and one squirrels, respectively. Evidently in Japan C. erythraeus carries relatively few ectoparasite species; this may be a contributory factor to their invasive success. Further investigations are needed to assess risks of zoonotic transmission of plague or murine typhus by C. anisus, of louse-borne typhus by N. callosciuri and of tularaemia and especially Japanese spotted fever (Rickettsia japonica) by H. flava.

Animals↗

Th1 and Th2 cytokine production is suppressed at the level of transcriptional regulation in Kawasaki disease.

To clarify the functional state of T cells in Kawasaki disease, we analysed mRNA expression levels of Th1/Th2 cytokines (IFN-gamma and IL-4) along with Th1/Th2-inducing transcription factors, T-bet and GATA-3, which play pivotal roles in the development of Th1 and Th2 cells, respectively. By real-time PCR, IFN-gamma mRNA levels in peripheral blood mononuclear cells (PBMNC) were significantly decreased in Kawasaki disease patients compared with those with measles, and tended to be lower than those in healthy controls. T-bet mRNA levels were significantly decreased in patients with Kawasaki disease compared with healthy controls. In addition, IL-4 and GATA-3 mRNA levels were significantly decreased in Kawasaki disease compared with healthy controls. Regulatory cytokine mRNA levels (TGF-beta and IL-10) were also decreased in Kawasaki disease. The mRNA levels of IFN-gamma showed a significant positive correlation with those of T-bet in Kawasaki disease. These results suggest that the suppressed function of Th1 and Th2, associated with the suppression of both T-bet and GATA-3 gene expression, may be one of the immunological characteristics of Kawasaki disease.

Child↗

Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis.

BACKGROUND: The authors reported a mutation, P1158S, of the human skeletal muscle sodium channel gene (SCN4A) in a family with cold-induced hypokalemic periodic paralysis (hypoKPP) and myotonia. OBJECTIVE: To identify mechanisms of temperature dependency in this channelopathy. METHODS: Using the amphotericin B perforated patch clamp method, sodium currents were recorded at 22 and 32 degrees C from the wild-type (WT) and P1158S mutant SCN4A expressed in tsA201 cells. Computer simulation was performed, incorporating the gating parameters of the P1158S mutant SCN4A. RESULTS: P1158S mutant SCN4A exhibited hyperpolarizing shifts in voltage dependence of both activation and inactivation curves at a cold temperature and a slower rate of inactivation than the WT. Computer simulation reproduced the abnormal skeletal muscle electrical activities of both paralysis at a low potassium concentration in the cold and myotonia at a normal potassium concentration. CONCLUSIONS: Both paralysis and myotonia are attributable to the biophysical properties of the SCN4A mutation associated with hypoKPP. This is the first report of an SCN4A mutation that exhibits temperature-dependent shifts of voltage dependence in sodium channel gating.

Action Potentials↗

Longitudinal growth and height velocity of Japanese children with Down's syndrome.

AIM: To determine the natural growth pattern of Japanese children with Down's syndrome. METHODS: Longitudinal height data of 85 patients (43 males, 42 females) from birth to final height were analyzed. Based on these data, semi-longitudinal standard growth curves and height velocity curves for Down's syndrome were drawn. RESULTS: The means +/- SD of final height of males and females with Down's syndrome were 153.2 +/- 5.6 and 141.9 +/- 4.2 cm, respectively. They were -3.0 SD and -2.8 SD for Japanese standards. Mean peak height velocities were 8.9 and 7.5 cm y(-1), and the ages at peak height velocity were 11.6 and 10.2 y for males and females, respectively. CONCLUSION: The mean height of patients with Down's syndrome was around -2 SD for normal children before puberty. Their pubertal growth spurt starts about 1 y earlier and their peak height velocity was about 1.3-1.4 cm shorter than for normal children.

Asian People↗

Peculiar bundles of filaments in Leydig cells of the lesser mouse deer (Tragulus javanicus): an ultrastructural study.

Leydig cells of lesser mouse deer (Tragulus javanicus) testes were observed using light and transmission electron microscopies. Sexually mature lesser mouse deer were obtained in East Malaysia. The testes were perfused with 5% glutaraldehyde, postfixed with 1% OsO4, dehydrated in ethanol and embedded in Araldite. The semithin sections were cut, stained with toluidine blue and observed under light microscopy. The ultrathin sections were cut, stained with uranyl acetate and lead citrate, and examined using a JEM-1200 transmission electron microscope. As a result, two types of filament bundles were frequently recognized in Leydig cells, but not in other testicular cells. These bundles were clearly seen at even a light microscopic level. One type was bundles of actin filaments (approximately 5 nm in diameter). These structures were found not only in the cytoplasm but also in the nucleus. The other type was bundles of intermediate filaments (approximately 10 nm in diameter). These structures were found only in the cytoplasm. The existence of filament bundles has never been reported in the testicular cells of another mammalian species. Thus, while bundles of actin and intermediate filaments are specifically present in the Leydig cells of the lesser mouse deer, their functions are still unclear.

Animals↗

Determination of bone volume by osteocyte population.

During development and growth, biological tissues and organisms can control their size and mass by regulating cell number (Raff, 1992; Conlon and Raff, 1999). Later in life both cell number and organ mass decrease (Buetow, 1985). We demonstrate that the number density of bone cells buried in the calcified matrix (osteocyte lacunar density) predicts extracellular matrix volume for both cancellous and cortical bone in a broad cross-section of the population (males and females, age range 23-91 years, r(2) = 0.98). Our hypothesis is that bone mass is determined by the control of osteocyte number, and that this is a particular instance of the control of organ size through the social controls on cell survival and death (Raff, 1992; Conlon and Raff, 1999).

Adolescent↗

Comparative functional morphology of the masticatory apparatus in the long-snouted crocodiles.

The masticatory muscles and their related structures of the skull were observed in the Indian gavial (Gavialis gangeticus), the false gavial (Tomistoma schlegelii), and the African slender-snouted crocodile (Mecistops cataphractus) to detail some morphological differences in comparison with the other crocodile species, and to compare and elucidate the functional strategy of themasticatory apparatus in these long-snouted species. The Musculus pterygoideus posterior was relatively smaller in the three species compared with many short-snouted crocodiles. It suggests that the masticatory power in fish-eating long-snouted species is not so high as in the short-snouted crocodiles, while the masticatory muscles were morphologically different among the three long-snouted species as follows. The M. pterygoideus posterior of the false gavial was extended in the lateral side of the lower jaw unlike the Indian gavial. The M. pseudotemporalis and the Fenestra supratemporalis were largely developed in the Indian gavial, however we suggest that the other two species possess the weak bundles in this muscle. The false gavial and the African slender-snouted crocodile have the pterygoid bone well-developed extending dorso-ventrally and it is suggested that the M. adductor mandibulae posterior attached to the pterygoid bone may be much larger than the Indian gavial. These data morphologically clarify the masticatory mechanism in the long-snouted crocodiles different from the short-snouted species, and demonstrate that the evolutional strategy to share the functional role in the masticatory muscles have been differently established between the Indian gavial and the other two species. We also obtained the morphological data in the fossil skull of the Machikane crocodile (Toyotamaphymeia machikanense) and concluded from the fossil characters that the considerable developments of the M.pterygoideus posterior and the M.pseudotemporalis in this species had not morphologically been consistent with both the Indian and false gavials.

Alligators and Crocodiles↗

Age related shift in the primary sites of involvement in cervical spondylotic myelopathy from lower to upper levels.

Ascending axonal volleys were analysed after epidural stimulation at multiple sites along the cervical cord to localise the site of the lesion precisely in cervical spondylotic myelopathy. The intraoperative recordings uncovered a single site of focal conduction block in 129 of 136 affected patients who underwent surgical intervention because of evidence of multilevel compression obtained by magnetic resonance imaging. Statistical analyses showed a shift of abnormalities from lower to upper cervical levels with advancing age (p < 0.0001). In particular, 92% of the oldest group (aged over 70 years) had localised dysfunction at C3-4 or C4-5, while 68% of patients aged under 60 years had lesions at C5-6 or C6-7.

Adult↗

Solid-Phase synthesis of a library constructed of aromatic phosphate, long alkyl chains and tryptophane components, and identification of potent dipeptide telomerase inhibitors.

Telomerase inhibitors are expected as a new candidate of therapeutic agents for cancer. Recently, we have found novel inhibitors based on the bisindole skeleton. In this study, solid-phase synthesis was applied to construct a library of inhibitors having aromatic phosphate, long alkyl chain and tryptophane components, from which a D,D-ditryptophane derivative has been identified as a new potent telomerase inhibitor with IC(50) values of 0.3 microM. A hypothetical binding model for the new inhibitors has been proposed based on the structure-activity relationship.

Dipeptides↗

Development of novel telomerase inhibitors based on a bisindole unit.

Telomerase is the enzyme that elongates telomere repeat at the ends of a chromosome. As high telomerase activity is observed in most cancer cells, inhibitors of human telomerase have been expected as new chemotherapeutic agents for cancer. We describe here the discovery of novel inhibitors with IC50 values in the submicromolar range. The structure of the novel inhibitors will be useful as a scaffold for construction of the library in the search for telomerase inhibitors.

Enzyme Inhibitors↗

Clonal evolution from trisomy into tetrasomy of chromosome 8 associated with the development of acute myeloid leukemia from myelodysplastic syndrome.

Tetrasomy 8, though rare, is usually associated with trisomy 8, a far more common chromosomal abnormality in acute myeloid leukemia (AML). Yet the clonal relationship between trisomy 8 and tetrasomy 8 in the cases with these chromosomal abnormalities has been unclear. Here, we report a case of a 17-year-old male, diagnosed as having a myelodysplastic syndrome (MDS). Chromosome analysis showed the presence of trisomy 8. Five years later, he developed overt AML exhibiting tetrasomy 8 only. After chemotherapy, the blast cells in the bone marrow decreased to 3.4%, and the karyotype showed trisomy 8 alone. Fluorescence in situ hybridization using a probe specific for chromosome 8 showed that the percentages of cells exhibiting 2/ 3 /4 signals were 7.8/89.2/2.0 at the MDS stage, 20.5/36.1/41.0 when overt AML developed and 24.0/72.1/2.4 after chemotherapy. These results suggested that tetrasomy 8 is derived from the AML clone, possibly evolved from the MDS clone with trisomy 8. To our knowledge, this is the first detailed case report of clonal evolution from trisomy 8 into tetrasomy 8 associated with the development of AML from MDS.

Adolescent↗

Inclusion body myositis: expression of extracellular signal-regulated kinase and its substrate.

OBJECTIVE: To assess abnormal intracellular signal transduction in inclusion body myositis (IBM). BACKGROUND: Mitogen-activated protein kinases (MAPKs) play pivotal roles in intracellular signal transduction and regulate cell growth and differentiation. Upon their activation, MAPKs translocate from the cytoplasm into the nucleus. DESIGN/METHODS: The authors investigated the localization of several forms of the MAPK family-extracellular signal-regulated kinase (ERK), c-Jun N-terminal protein kinase (JNK), and p38 MAPK (p38)-in 10 patients with sporadic IBM and in 52 control subjects. The relationship between the localization of immunopositive deposits and nuclei was tested with bis-benzimide. RESULTS: Vacuolated fibers in IBM displayed very strong focal immunoreactivity of ERK, but not of JNK or p38. The ERK-positive deposits in these vacuolated fibers colocalized with the nuclear substrate of ERK, Elk-1. ERK- and Elk-1-positive deposits were located frequently on the surface of the nuclei in vacuolated fibers in IBM. Similar findings to those of sporadic IBM were observed in three patients with distal myopathy with rimmed vacuoles, but not in eight normal or the other 41 disease controls. CONCLUSION: There is evidence for impaired molecular transport to the nucleus from the cytoplasm in the vacuolated fibers in IBM. This could be due to cytoplasmic aggregation of ERK and Elk-1 or to abnormal nuclear pore machinery involved in the transport of ERK and its substrate upon ERK activation.

Adult↗

Sequential changes of orthodromic sensory nerve action potentials induced by experimental compression of the median nerve at the wrist.

OBJECTIVE: We studied sequential waveform changes associated with a progressive conduction block to elucidate the relative vulnerability of slow versus fast conducting fibers to a focal compression. METHODS: In 12 healthy men, orthodromic compound sensory nerve action potentials (SNAPs) of the median nerve were recorded unipolarly at 4 sites over the forearm during a 30 min period of constant, localized compression of the nerve at the wrist. RESULTS: Initial findings at the compression site consisted of nearly immediate reduction in size of the negative component accompanied by progressive enlargement of the initial-positive component. Recording at 2 cm proximal to the compression and at the elbow showed no change in onset latency initially, indicating at least partial preservation of the fast conducting fibers. Amplitude also remained unchanged for about 20 min, presumably because loss of negative and positive peaks compensated each other until conduction block began to involve a greater number of the fast conducting fibers. CONCLUSIONS: The analysis of waveform changes and their time course suggests that a focal compression initially affects the slow conducting small diameter fibers. Partial conduction block gives rise to complex waveform changes depending on recording sites. A reduction in one polarity of constituent nerve fiber action potentials may enhance the other polarity of the SNAP.

Action Potentials↗

Influence of nonenzymatic glycation on biomechanical properties of cortical bone.

In this study, the influence of nonenzymatic glycation (NEG) on the mechanical properties of bone and bone collagen were investigated. Bovine cortical bone specimens were incubated in ribose to cause collagen cross-links in vitro, and nondestructive mechanical testing was used to determine tensile and compressive elastic modulus as a function of incubation time. Mechanical properties associated with yield, postyield, and final fracture of bone were determined at the end of the incubation period. The stiffness of the collagen network was measured using stress relaxation tests of demineralized bone cylinders extracted periodically throughout the incubation period. It was found that accumulation of nonenzymatic glycation end-products in cortical bone caused stiffening of the type I collagen network in bone (r2 = 0.92; p < 0.001) but did not significantly affect the overall stiffness of the mineralized bone (p = 0.98). The ribosylated group had significantly more NEG products and higher yield stress and strain than the control group (p < 0.05). Postyield properties including postyield strain and strain energy were lower in the ribosylated group but were not significantly different from the control group (p = 0.24). Compared with the control group, the ribosylated group was characterized by significantly higher secant modulus and lower damage fraction (p < 0.05). Taken together, the results of this study suggest that collagen in bone is susceptible to the same NEG-mediated changes as collagen in other connective tissues and that an increased stiffness of the collagen network in bone due to NEG may explain some of the age-related increase in skeletal fragility and fracture risk.

Animals↗