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Biomedical subjects

H Imai

Publications and source records attributed to H Imai.

At least 181 records · Page 10Linked to original sources

Heart rate variability during chemical thoracic sympathectomy.

BACKGROUND: Chemical thoracic sympathectomy (CTS) resulted in profound bradycardia in a patient with severe post-therapeutic neuralgia. To clarify the cause of this bradycardia, the authors evaluated heart rate variability using a Poincaré plot, which is a scatter diagram of the current R-R interval plotted against the R-R interval immediately preceding it, in this patient and in others scheduled for CTS or mandibular block (MB). METHODS: Twenty-three patients were scheduled for CTS (n = 13, CTS group) and for MB (n = 10, MB group). Heart rate and the SD of the R-R interval variabilities spreading along the x axis (SDRR) and perpendicularly along the diagonal line of the Poincaré plot (SDdeltaRR) were evaluated before, just after, and 1 h after the block. RESULTS: Neither group had significant changes in heart rate. The MB group showed no significant change in the SD(RR):SDdeltaRR ratio. In the CTS group, however, the SD(RR):SDdeltaRR ratio decreased significantly from 1.72+/-0.20 to 1.23+/-0.11 just after CTS. The previous patient, who had a high SD(RR):SDdeltaRR ratio of 3.45 before CTS, exhibited severe bradycardia (22 beats/min). CONCLUSIONS: The SD(RR):SDdeltaRR ratio decreased after CTS without any significant concomitant change in heart rate. The decrease in the SD(RR):SDdeltaRR. ratio indicates a reduction of cardiac sympathetic activity. However, CTS in patients having high SD(RR):SDdeltaRR ratios can result in profound bradycardia.

Adult↗

Contribution of foregut endoderm to tooth initiation of mandibular incisor in rat embryos.

Classical transplantation experiments with various amphibian tissues have shown that tooth development requires not only oral ectoderm and neural crest but also foregut endoderm. In addition, histological observation of oral membrane showed that the tooth germs are initiated in some ectodermal cells and neural crest cells adjacent to foregut endoderm. These studies suggest that tooth initiation requires the presence and cooperation of these three components. In mammals, however, there is no direct evidence that tooth formation is involved in the region of oral ectoderm adjacent to foregut endoderm. In order to elucidate the contribution of foregut endoderm to tooth formation, we established a new type of endodermal cell tracing system with a recombinant adenovirus called Adex-lacZ, and performed endodermal cell tracing in a long-term culture system. Cells labelled with Adex-lacZ were seen next to non-labelled thickening epithelium, presumptive incisor epithelium. These findings show the first direct evidence in mammals that tooth formation takes place in the specified part of oral ectoderm adjacent to foregut endoderm, suggesting that foregut endoderm plays a role in tooth initiation.

Adenoviridae↗

Decreased physical performance of congenic mice with mismatch between the nuclear and the mitochondrial genome.

Maternal transmission of mitochondrial DNA (mtDNA) allows us to generate mtDNA congenic strain by repeating backcrosses of female mice to male mice of an inbred strain, which carries different mtDNA haplotype from that of the female progenitor. Since genetic backgrounds of inbred strains commonly used (e.g., C57BL/6J [B6] and BALB/c) are mainly derived from an European subspecies of Mus musculus domesticus, congenic strains, in which mtDNA originated from an Asian subspecies M. musculus musculus or an European species M. spretus, give in vivo condition that mismatch occurs between the mitochondrial and the nuclear genome. So far, little has been known how the mismatch condition affects the physiological phenotype of the mice. To address this question, we established two mtDNA congenic strains, C57BL/6J(B6)-mtSPR and BALB/c-mtSHH, which carry M. spretus- and M. m. musculus-derived mtDNAs, representing the conditions of interspecific and intersubspecific mitochondrial-nuclear genome mismatch, respectively. Using these congenic strains, we examined their physical performance by measuring their running time on a treadmill belt until exhaustion. The result clearly showed that the mtDNA congenic strains manifested a significant decrease in the level of physical performance, when compared with their progenitor strains. It also appeared that the congenic mice manifested growth rate. Thus, all results indicated that mismatch between the mitochondrial and the nuclear genome causes phenotypic changes in individuals of mice.

Animals↗

Improvement of the A(*) Algorithm for Multiple Sequence Alignment.

The alignment problem of DNA or protein sequences is very applicable and important in various fields of molecular biology. This problem can be reduced to the shortest path problem and Ikeda and Imai (Genome Informatics 5: 90-99, 1994) showed that the A(*) algorithm works efficiently with the estimator utilizing all 2-dimensional sub-alignments. In this paper we present new powerful estimators utilizing k >/= 3 dimensional sub-alignments, and propose a new bounding technique using V (Delta), a set of vertices in the paths whose lengths are at most Delta longer than the shortest path. We also extend our algorithm to a recursive-estimate version. These algorithms become more efficient when the number of sequences increase, or the similarity among sequences is lower.

Journal Article↗

Interleukin-1 receptor antagonist inhibits transient increase of plasma corticosterone in the initial phase of trimethyltin-induced hippocampal necrosis.

The temporal increase of plasma corticosterone (CORT) levels at 3 or 4 days after a single oral administration of trimethyltin (TMT) was suppressed by intracerebroventricular administration of the interleukin-1 receptor antagonist (IL-1ra). On the other hand, glutamate receptor antagonist (MK801) did not affect the TMT-induced CORT level increase. These results indicate that this transient activation of the hypothalamo-pituitary-adrenocortical axis in TMT-treated rats may be in part attributable to the neuroendocrine effects of IL-1 produced by microglia.

Administration, Oral↗

[Color Doppler signal enhancement with SH/TH-508 in pancreatic tumors].

In this report, we showed the efficacy of a new contrast agent (SH/TA-508, Schering AG, Germany) for color Doppler imaging of the pancreatic tumors. In pancreatic ductal cancer, no enhancement of the lesion was observed, but vascular invasion by cancer became to be easily evaluated. On the other hand, hypervascular tumors such as islet cell tumor and cystadenocarcinoma, were increased in color Doppler signals of vessels by SH/TA-508. We concluded that SH/TA-508 was useful for evaluating the vascular invasion by pancreatic cancer as well as vascularity of hypervascular mass and solid component of cystic neoplasma.

Adenoma, Islet Cell↗

Cost analysis of treatments for severe combined immunodeficiency patients caused by adenosine deaminase deficiency: comparison of gene therapy and bone marrow transplantation.

In order to perform a cost assessment of treatment for severe combined-immunodeficiency patients caused by adenosine deaminase deficiency, we estimated the cost for 3 successfully treated patients in Japan for whom related HLA-identical bone marrow donors could not be found. One patient received gene therapy and the other 2 patients received HLA-haploidentical bone marrow transplantation. The medical costs required for hospitalization periods for gene therapy and bone marrow transplantation were estimated respectively by analyzing the monthly bills that were calculated based on the fee schedule covered by health insurance. In the gene therapy, the total cost was calculated by adding the charges not covered by health insurance. The gene therapy and transplantation patients had significant differences in terms of cost structure and total cost. The items concerning "procedures" associated with gene transduction in the former amounted to 47.8% of the total cost, and "medication" in the latter amounted to 34.3% and 31.9% respectively. The items concerning "hospitalization" amounted to a large percentage in both treatments. The total cost was estimated at approximately 18.9 million yen for gene therapy, and 7.4 million yen and 10.5 million yen for transplantation. These results obtained through this study revealed the cost structure of gene therapy in comparison with transplantation. This report represents the first step to the assessment of medical technology of human gene therapy, in terms of medical cost, in which a stable and favorable therapeutic outcome was achieved.

Adenosine Deaminase↗

[A patient with focal bi-parietal atrophy presenting motor clumsiness and cortical sensory loss].

We report a 73-year-old woman who presented progressive motor clumsiness, cortical sensory loss, and focal parietal lobe atrophy. She was well until one year prior to the present admission when she suffered from what appeared to be mild Fisher syndrome from which she showed excellent recovery. However, soon she noted a gradual onset of difficulty in hand movements and in the recognition of objects by hands. Neurologic examination revealed an alert and well oriented Japanese woman without dementia. Cranial nerves were unremarkable. Although, she did not have aphasia, apraxia, or agnosia, she showed marked clumsiness in skilled hand movements such as using chopsticks, hand writing, and buttoning. She had no motor weakness, ataxia, rigidity, or spasticity. Deep tendon reflexes were symmetrically diminished. Sensory examination revealed cortical sensory loss such as disturbances of two point discrimination, weight sensation, and stereotactic sensations. Her motor clumsiness appeared to be caused by her cortical sensory loss. MRI revealed marked focal atrophy in the bilateral parietal lobe, particularly in the postcentral gyrus and the adjacent association areas. Recently, neurodegenerative disorders with focal brain atrophy such as corticobasal degeneration, Pick's disease, and dementia of frontal lobe type have been reported, however, our patient does not fit to any of these known disorders nor clinical features are distinctly different from Alzheimer's disease. Our patient may be another example of progressive cerebral degeneration with emphasis on the parietal cortex.

Aged↗

[Intraoperative transient incomplete left bundle branch block in a patient with left axis deviation in pre-anesthetic electrocardiogram].

We encountered a case of transient incomplete left bundle branch block (TILBBB) during standard mastectomy under general anesthesia. The patient was a 40 year-old female (70 kg, 164 cm) without any abnormalities on preanesthetic examinations except -61 degrees left axis deviation in exercise electrocardiogram. Adriamycin 20 mg was administered preoperatively. After the skin incision, heart rate increased from 104 min-1 to 130 min-1 and the cardiac axis gradually rotated leftward with increasing Q wave depth on leads I and aVL. We diagnosed this as blockade of the anterior branch in the left bundle branch. After the administration of fentanyl (0.2 mg) and sevoflurane (3%), the heart rate decreased to 105 min-1 and the electrocardiogram returned to the initial wave form. This anesthetic course indicated that adriamycin had slightly damaged the cardiac muscle and inadequate anesthesia had caused tachycardia and transient left bundle branch block. Left axis deviation on preoperative exercise electrocardiogram suggests that the left bundle branch can easily be blocked with an increasing heart rate. Adequate depth of anesthesia would have prevented the increase in heart rate and abnormality in the cardiac conduction process.

Adult↗

Presence of two rhodopsin intermediates responsible for transducin activation.

To identify how many rhodopsin intermediates interact with retinal G-protein transducin, the photobleaching process of chicken rhodopsin has been investigated in the presence or absence of transducin by means of time-resolved low-temperature spectroscopy. Singular value decomposition (SVD) analysis of the spectral data showed that a new intermediate called meta Ib is present between formally identified metarhodopsin I (now referred to as meta Ia) and metarhodopsin II (meta II). Since the absorption maximum of meta Ib (460 nm) is similar to that of meta Ia (480 nm), but considerably different from that of meta II (380 nm), meta Ib should have a protonated retinylidene Schiff base as its chromophore. Whereas transducin showed no effect on the conversion process between lumirhodopsin (lumi) and meta Ia, it affected the process between meta Ia and meta Ib and that between meta Ib and meta II. These results suggest that at least two intermediates (meta Ib and meta II) interact with transducin. The addition of GTPgammaS had no effect on the meta Ib-transducin interaction, while it abolished the ability of transducin to interact with meta II. Thus, meta Ib only binds to transducin, while meta II catalyzes a GDP-GTP exchange in transducin. These results suggest that deprotonation of the Schiff base chromophore is not necessary for the binding to transducin, while changes in protein structure including Schiff base deprotonation are needed to induce the GDP-GTP exchange in transducin.

Animals↗

Dimethoxyphenylethylamine and tetrahydropapaverine are toxic to the nigrostriatal system.

We report the toxic effects of 3,4-dimethoxyphenylethylamine (DMPEA), and tetrahydropapaverine (THP) on the rat nigrostriatal system; THP is a tetrahydroisoquinoline compound which may be derived from DMPEA by conjugation of DMPEA and its oxidative metabolite, dimethoxyphenylacetaldehyde; both are potent inhibitors of mitochondrial complex I. These compounds were introduced to the unilateral caudate-putamen of male Sprague-Dawley rats over 7 days using a 200-microl mini-osmotic pump. Striatal dopamine on the injected side showed a significant decrease to 86% of the non-injected side after 16.55 micromol/7 days infusion of DMPEA, and to 73% of the non-injected side after 7.90 micromol/7 days of THP infusion; as the non-injected side dopamine also reduced in the THP-injected rats, dopamine on the injected side was 55% of the saline control. Tyrosine hydroxylase (TH)-positive nigral neurons were decreased to 76% of the non-injected side after 16.55 micromol/7 days infusion of DMPEA and to 77% after 7.90 micromol/7 days of THP infusion. Dimethoxyphenyl-tetrahydroisoquinoline compounds appear to be potent nigral neurotoxins.

3,4-Dihydroxyphenylacetic Acid↗

Photochemical and biochemical properties of chicken blue-sensitive cone visual pigment.

Through low-temperature spectroscopy and G-protein (transducin) activating experiments, we have investigated molecular properties of chicken blue, the cone visual pigment present in chicken blue-sensitive cones, and compared them with those of the other cone visual pigments, chicken green and chicken red (iodopsin), and rod visual pigment rhodopsin. Irradiation of chicken blue at -196 degrees C results in formation of a batho intermediate which then converts to BL, lumi, meta I, meta II, and meta III intermediates with the transition temperatures of -160, -110, -40, -20, and -10 degrees C. Batho intermediate exhibits an unique absorption spectrum having vibrational fine structure, suggesting that the chromophore of batho intermediate is in a C6-C7 conformation more restricted than those of chicken blue and its isopigment. As reflected by the difference in maxima of the original pigments, the absorption maxima of batho, BL, and lumi intermediates of chicken blue are located at wavelengths considerably shorter than those of the respective intermediates of chicken green, red and rhodopsin, but the maxima of meta I, meta II, and meta III are similar to those of the other visual pigments. These facts indicate that during the lumi-to-meta I transition, retinal chromophore changes its original position relative to the amino acid residues which regulate the maxima of original pigments through electrostatic interactions. Using time-resolved low-temperature spectroscopy, the decay rates of meta II and meta III intermediates of chicken blue are estimated to be similar to those of chicken red and green, but considerably faster than those of rhodopsin. Efficiency in activating transducin by the irradiated chicken blue is greatly diminished as the time before its addition to the reaction mixture containing transducin and GTP increases, while that by irradiated rhodopsin is not. The time profile is almost identical with those observed in chicken red and green. Thus, the faster decay of enzymatically active state is common in cone visual pigments, independent of their spectral sensitivity.

Animals↗

Minisatellite instability in severe combined immunodeficiency mouse cells.

We have recently found that okadaic acid, which shows strong inhibitory activity on protein serine/threonine phosphatases and tumor-promoting activity in vivo and in vitro, induces minisatellite mutation (MSM). Human tumors and chemically induced counterparts in experimental animals are also sometimes associated with MSM. In the present study, we demonstrated minisatellite (MS) instability in severe combined immunodeficiency (SCID) cells in which the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is impaired. Cells from a SCID fibroblast cell line transformed by simian virus 40 large tumor antigen, SC3VA2, and from an embryonal SCID fibroblast cell line, SC1K, were cloned and propagated to 10(7) to 10(8) cells, and then subjected to subcloning. After propagation of each subclone to 10(7) to 10(8) cells, DNA samples were digested with HinfI and analyzed by Southern blotting using the Pc-1 MS sequence as a probe. Under low-stringency conditions, about 40 MS bands were detected, with 45% +/- 6% and 37% +/- 3% of SC3VA2 and SC1K cells, respectively, having MSM. In contrast, cells from the RD13B2 cell line, which was established from SCVA2 by introducing human chromosome 8q fragments, on which DNA-PKcs is known to reside, to complement the SCID phenotype, showed a very low frequency of MSM (3% +/- 3%). The high frequencies of MSM in SC3VA2 and SC1K were significant, with no difference between the two. The present study clearly demonstrates that MS instability exists in SCID fibroblasts, suggesting that DNA-PKcs might be involved in the stable maintenance of MS sequences in the genome.

Animals↗

Identification of a chick homologue of Fringe and C-Fringe 1: involvement in the neurogenesis and the somitogenesis.

In Drosophila, Serrate plays an important role to the wing margin formation. A putative secretory protein, Fringe, is indispensable for the wing margin formation inducing Serrate and other genes. Recently, Xenopus homologues of Fringe were identified and one of them, lunatic Fringe (X-lFng), was demonstrated to be involved in mesoderm induction. We have identified two chick Fringe homologous genes by reverse transcription-polymerase chain reaction and cDNA library screening. One of them, C-Fringe 1, showed sequence similarity to X-lFng. In situ hybridization study of C-Fringe 1 has demonstrated its expression in the developing nervous system and in the presomitic mesoderm. The hindbrain and spinal cord showed the distinct stripe pattern expression which was complementary to that of C-Serrate, indicating the correlation between them in vertebrate.

Amino Acid Sequence↗

Excitotoxic lesions of the pedunculopontine tegmental nucleus produce contralateral hemiparkinsonism in the monkey.

Dopaminergic nigrostriatal neurons, degeneration of which causes Parkinson's disease, are known to receive excitatory input almost exclusively from the pedunculopontine tegmental nucleus (PPN). We report here that excitotoxic lesions of the PPN produce abnormal motor signs relevant to hemiparkinsonism in the macaque monkey. Under the guidance of extracellular unit recordings, the electrophysiologically identified PPN was injected unilaterally with kainic acid. These PPN-lesioned monkeys exhibited mild to moderate levels of flexed posture and hypokinesia in the upper and lower limbs contralateral to the lesion. In most of the monkeys, such pathophysiological events were gradually improved and became stationary in 1-2 weeks. The hemiparkinsonian symptoms observed after PPN destruction might be ascribed to a decrease in nigrostriatal neuron activity due to excitatory input ablation.

Animals↗