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Biomedical subjects

T Komiyama

Publications and source records attributed to T Komiyama.

At least 55 records · Page 3Linked to original sources

Identification of a novel polymorphism of the human dopamine transporter (DAT1) gene and the significant association with alcoholism.

Human dopamine transporter gene (DAT1) has a variable number of tandem repeats (VNTR) in its 3'-untranslated region (UTR). The association between the VNTR polymorphism and neuropsychiatric disorders has been studied, but their relationship is still unclear. Here we identified a novel polymorphism in the 3'-UTR of the DAT1 gene, G2319A, and a significant association between the polymorphism and alcoholism was observed in both genotypic and allelic frequencies (P = 0.040 and 0.019, extended Fisher's exact test, respectively). There was a significant gene dose effect on the risk for alcoholism associated with the 2319-A allele (chi2 = 6.16, df = 2, P = 0.046, linearity tendency test: Cochranq-Armitage analysis). Moreover, in the haplotype analysis with G2319A- and VNTR-polymorphisms, a positive gene dose efffect on the risk with the A10 allele (P = 0.044, linearity tendency test) and a negative gene dose effect with the G10 allele (P = 0.010, linearity tendency test) for alcoholism were significantly detected. Odds ratio for alcoholism with the A10 and G10 alleles were 1.76 (1.12-2.76) and 0.53 (0.32-0.79), respectively. These results indicate that the DAT1 gene may confer vulnerability to alcoholism.

3' Untranslated Regions↗

[Evaluation of two-dimensional thick-slice MR DSA: preliminary study].

We have used two-dimensional contrast-enhanced MR angiography for a single thick slice and called it MR DSA. This technique realizes nearly subsecond scanning per image and is therefore superior to other types of contrast-enhanced MR angiography in temporal resolution. To determine the optimal parameters of this technique, we calculated SSR (the signal of brain to the signal of contrast agent ratio) in various settings. We also obtained MR DSA images of 26 cases. We believe that MR DSA may play a supportive role in conventional MR imaging or angiography, since its high temporal resolution is of value in the evaluation of cerebrovascular diseases.

Angiography, Digital Subtraction↗

Comparison of near-infrared spectroscopy with air plethysmography in detection of deep vein thrombosis.

BACKGROUND: As a noninvasive screening test, air plethysmography (APG) is a reliable and frequently used modality in the detection of deep vein thrombosis (DVT). Although APG is highly sensitive for the diagnosis of proximal DVT, its sensitivity for identifying calf DVT is poor. Near-infrared spectroscopy (NIRS) is a new modality which can be used to evaluate venous retention during walking. The purpose of this study was to investigate the diagnostic value of NIRS for the detection of DVT, particularly isolated calf DVT, in comparison with APG. METHODS: Fifty limbs of 39 consecutive patients with clinically suspected DVT were studied. All patients were examined by venography and APG. Patients also underwent a treadmill-walking test with simultaneous NIRS. Deoxygenated hemoglobin was continuously measured by NIRS during exercise. The ambulatory venous retention index obtained from serial DeoHb changes was calculated in each patient. RESULTS: Venography demonstrated DVT in 35 limbs, confined to the calf in 9 limbs, and with the involvement of a proximal deep vein with thrombi in 26. The overall sensitivity of NIRS and APG was 97% (34/35) and 80% (28/35), respectively. NIRS was more sensitive than APG for detecting isolated calf DVT (89% [8/9] and 22% [2/9], respectively), while both tests identified proximal DVT in all limbs. CONCLUSIONS: NIRS is a highly sensitive method for the diagnosis of haemodynamically significant DVT. NIRS may become a useful screening test because of its reliability in detecting calf vein thrombi that cannot be identified by APG.

Female↗

Organ/Tissue absorbed doses measured with a human phantom torso in the 9th Shuttle-Mir Mission (STS-91).

Organ/Tissue absorbed doses were measured with a life-size human phantom torso in the 9th Shuttle/Mir Mission (STS-91) from June 2 to 12, 1998. This is the first attempt to measure directly organ/tissue doses over a whole human body in space. The absorbed dose was measured by combination of two integrating detectors: thermo- luminescent dosemeter of Mg2SiO4: Tb (TDMS) and plastic nuclear track detector (PNTD). Both detectors were calibrated on ground using high-energy charged-particle beams. The detectors were packed in 59 cases of tissue-equivalent resin; and put into the positions of radiologically important organs and tissues in the phantom. Efficiency reductions of TDMS for high-LET particles were corrected based on the LET-differential particle fluence of space radiation measured with PNTDs. The accumulated absorbed doses during this 9.8-days mission at low-earth orbit (400 km x 51.6 degrees) ranged from 1.6 mGy at colon to 2.6 mGy at bone surface (shoulder) with a variation factor of 1.6. The absorbed doses at some internal organs were higher than the skin dose. This fact is important from the viewpoint of radiological protection for astronauts.

Cosmic Radiation↗

Aberrant processing of wild-type and mutant bovine pancreatic trypsin inhibitor secreted by Aspergillus niger.

Bovine pancreatic trypsin inhibitor (BPTI) was secreted by Aspergillus niger at yields of up to 23 mg l-1 using a protein fusion strategy. BPTI was linked to part of the fungal glucoamylase protein (GAM) with a dibasic amino acid (KEX2) processing site at the fusion junction. Electrospray ionisation mass spectrometry and N-terminal protein sequencing revealed that, although biologically active in vitro, the purified products from a number of independent transformants consisted of a mixture of BPTI molecules differing at the N-terminus. Approximately 35-60% of this mixture was processed correctly. Aberrant processing of the GAM-BPTI fusion protein by the A. niger KEX2-like endoprotease was the most likely cause of this variation although the involvement of other fungal endoproteases could not be ruled out. In vitro studies have highlighted a weak interaction between BPTI and the Saccharomyces cerevisiae KEX2 endoprotease, suggesting that BPTI is not a potent inhibitor of KEX2p. A small proportion of the recombinant BPTI (10%) showed 'nicking' of the K15-A16 bond, indicating an interaction with a fungal trypsin-like enzyme. Mutant BPTI homologues designed to have anti-elastase activity, BPTI(K15V), BPTI(K15V,P13I) and BPTI(K15V,G12A), have also been expressed and secreted by A. niger. They also showed a similar spectrum of aberrant N-terminal processing but no 'nicking' of the K15-V16 bond was observed. Comparison of A. niger with other expression systems showed that it is an effective system for producing BPTI and its homologues, although not all molecules were correctly processed. This variation in processing efficiency may be useful in understanding the important determinants of protein processing in this fungus.

Amino Acid Sequence↗

Useful 1O2 (1delta g) generator, 3-(4'-methyl-1'-naphthyl)-propionic acid, 1',4'-endoperoxide (NEPO), for dioxygenation of squalence (a skin surface lipid) in an organic solvent and bacterial killing in aqueous medium.

3-(4'-Methyl-1'-naphthyl)-propionic acid, 1',4'-endoperoxide (NEPO) provides singlet state of oxygen (1O2, 1delta g) at 37 degrees C in sodium phosphate buffer (pH 7.2), acetate buffer (pH 4.5), methanol or chloroform, through the retro-Diels-Alder reaction. The total amount of 1O2 generated by NEPO was calculated using the following equation: [1O2]= [NEPO]0[1-exp(-kt)], where [1O2], [NEPO]0 and k are the total amount of 1O2 produced during the time t, initial concentration of NEPO and the first-order reaction rate constant, respectively. When squalene was exposed to 1O2 which was generated thermolytically from NEPO, it was oxidized to three hydroperoxides, mono-, di- and tri-hydroperoxides, in amounts proportional to the dose of NEPO. The oxidizability of squalene was much more extensive compared with unsaturated phospholipids. Additionally, when wild-type E. coli and lycopene-producing mutant E. coli were exposed to NEPO-derived 1O2, there was significant loss of viability of wild-type E. coli but no significant loss of viability in lycopene-producing strain, suggesting that lycopene by scavenging 1O2 protected E. coli against 1O2 toxicity.

Anti-Bacterial Agents↗

Function of sural nerve reflexes during human walking.

1. The functions of ipsilateral cutaneous reflexes were studied with short trains of stimuli presented pseudorandomly to the sural nerve during human walking. Electromyograms (EMG) of lower (tibialis anterior (TA), soleus, lateral (LG) and medial (MG) gastrocnemius) and upper leg (vastus lateralis and biceps femoris) muscles were recorded, together with ankle, knee and hip joint angles. Net reflex EMG responses were quantified in each of the sixteen parts of the step cycle. The kinematic measurements included ankle eversion- inversion, and ankle, knee and hip flexion-extension. 2. The function of the sural reflexes depended upon the part of the step cycle in which the nerve was stimulated and the intensity of stimulation. During stance, reflexes in MG and TA muscles in response to a medium intensity of stimulation (1.9 x radiating threshold, x RT) were closely associated with ankle eversion and dorsiflexion responses, respectively. These responses could assist in accommodation to uneven terrain that applies pressure to the lateral side of the foot (sural innervation area). Non-noxious, high intensity (2.3 x RT) stimulation resulted in strong suppression of LG and MG during stance which was correlated to a small reduction in ankle plantarflexion. At this higher intensity the response would function to prevent the foot from moving more forcefully onto a potentially harmful obstacle. 3. During swing, ankle dorsiflexion increased and was significantly correlated to the net TA EMG response after both medium and high intensity stimulation. Knee flexion was increased throughout swing at both intensities of stimulation. These responses may serve in an avoidance response in which the swing limb is brought past an obstacle without destabilizing contact. 4. The net EMG and kinematic responses suggest that cutaneous reflexes stabilize human gait against external perturbations produced by an uneven surface in stance or obstacles encountered during swing.

Adult↗

Plant defense-related enzymes as latex antigens.

BACKGROUND: Latex allergy is an increasing hazard to people who frequently come into contact with latex products. Of interest concerning this immediate-type allergy is the cross-reactivity to various vegetable foods and pollen. Despite its high prevalence, no adequate explanation has been provided for the cross-reactive antigens. OBJECTIVE: We have hypothesized that a series of plant defense-related proteins act as latex allergens, as well as vegetable food allergens. To evaluate this hypothesis, hydrolytic enzymes that are very likely to take on defensive roles in rubber trees were examined for their antigenicity. METHODS: By applying chromatographic procedures, defense-related enzymes were separated from nonammoniated latex (NAL). Their antigenicity was examined by immunoblotting and ELISA with sera containing IgE antibodies to crude latex proteins. RESULTS: Three kinds of hydrolytic enzymes (basic beta-1,3-glucanases [35, 36.5, and 38 kd], a basic chitinase/lysozyme [29.5 kd], and an acidic esterase [44 kd]) were separated from NAL. They were recognized by IgE antibodies from a significant number of patients allergic to latex. The basic beta-1,3-glucanases and the acidic esterase were also strongly recognized by IgE antibodies from several atopic subjects who were allergic to various vegetable foods rather than latex products. CONCLUSION: It was ascertained that the three defense-related enzymes separated from NAL constituted part of the latex antigens. Taking together the well-known serologic or immunologic relationships and amino acid sequence similarities of defense-related proteins coming from phylogenetically distant plant species, we can suspect their universal antigenicity and cross-reactivity.

Chitinases↗

Action properties of HYI killer toxin from Williopsis saturnus var. saturnus, and antibiotics, aculeacin A and papulacandin B.

The mechanism of the killing and cytocidal effects produced by HYI toxin from Williopsis saturnus var. saturnus, and by the amphiphilic antibiotics aculeacin A and papulacandin B on yeast Saccharomyces bayanus cells was studied. When the yeast cells were treated with these molecules, a discharge of cell materials at the budding position was observed by phase-contrast and scanning electron microscopy. The cytocidal effect of these molecules was most pronounced when the cells were in the logarithmic growth phase. Washing the HYI toxin incubation mixture completely eliminated the killing activity, but in the case of the antibiotics, it only partially reduced the cytocidal activity. Full recovery of the killing activity in the supernatant of the washing solution was observed after HYI toxin incubation, but in the case of the antibiotics, the recovery of cytocidal activity was time-dependent. The activity of membrane beta-1,3-glucan synthase was potently inhibited by HYI toxin, and the concentration of this enzyme in the budding tip was observed. These results suggest that HYI toxin exerts a cytocidal effect on the budding of sensitive yeast cells by inhibiting cell wall synthesis. This mechanism is similar to that of the HM-1 toxin of W. saturnus var. mrakii, and to aculeacin A and papulacandin B, although there are some differences from that of HYI toxin.

Aminoglycosides↗

Endothelial outgrowth and the subsequent cell transition in the culture of embryonic atrioventricular canal placed in an inverted polarity.

Endothelial cells in the atrioventricular (AV) segment of the developing chicken heart undergo a transition into mesenchymal cells. When the AV segment is explanted onto a hydrated collagen gel, endothelial cells grow out and reproduce in vivo cell transition regardless of the precise orientation of the explant on a gel. Our results showed that when the luminal side of an explant was placed towards a gel surface, the inverted polarity of endothelium was not adjusted by direct reorganization of polarity, but that the endothelium crawled down so as to settle on a gel surface in the correct original cell polarity. Subsequently, endothelial cells showed cytoplasmic hypertrophy, formed microvillous projections and then extended filopodial migratory appendages. These cellular changes were quite similar to those in vivo. However, the continuity of the endothelial layer was specifically disrupted in AV explant cultures. Such disruption was never observed in ventricle explant cultures in which endothelial-mesenchymal cell transition did not occur. The disintegration of AV endothelial outgrowth must be closely related to its capability to transform into mesenchymal cells and mitotic activity to keep a depository of endothelial cells.

Animals↗

[Nerve paralysis after third molar extraction].

This paper described the incidence of inferior alveolar nerve paralysis following surgical removal of impacted third molars. The investigated cases were 789 patients with 1,299 teeth that were surgically extracted. Eight (0.6%) patients had the inferior alveolar nerve paralysis and one (0.08%) had lingual nerve paralysis. As for the patients with inferior alveolar nerve paralysis, the incidence was 0.4% in those aged 20 to 29 years, 0.6% in those aged 30 to 39 years, and 3.5% in those aged over 40 years. This study showed that the incidence of inferior alveolar nerve paralysis occurred more frequently in older age cases and in the cases in which the root splitting or the removing the surrounding bone was needed.

Adult↗

Changes in the H-reflexes of ankle extensor and flexor muscles at the initiation of a stepping movement in humans.

The underlying neural mechanisms of the silencing of electromyographic (EMG) activity observed between antagonistic muscles of the human ankle joint preceding a fast stepping movement were examined. Twelve subjects were asked to perform a unilateral stepping movement under a reaction time condition while standing upright. A silent phase (SP) which was composed of the time difference between the offset of tonic soleus (Sol) activity and the onset of phasic tibialis anterior (TA) activity was observed consistently in all subjects. At the time interval corresponding to the SP, inhibition of the Sol Hoffmann reflex (H-reflex) and facilitation of the TA H-reflex took place. In nine of the 12 subjects, disynaptic reciprocal Ia inhibition (Ia inhibition) from TA Ia fibers to the Sol motoneuron (MN) pool increased before the TA EMG onset. We also observed a clear distinction between the changes in the time course of the Ia inhibition and that of long latency reciprocal (D1) inhibition in six of the 12 subjects. However, when the subjects performed the same motor task with their backs supported against a wall wherein the tonic Sol activation disappeared, no changes in the H-reflex occurred. These results suggest that these changes, occurring at the segmental level, might be controlled by the supraspinal motor center in a feed-forward manner during anticipatory postural adjustment. The functional significance would be to counterbalance the disturbance from an intentional forthcoming movement in order to maintain an adequate posture.

Adult↗

A novel yeast gene, RHK1, is involved in the synthesis of the cell wall receptor for the HM-1 killer toxin that inhibits beta-1,3-glucan synthesis.

The HM-1 killer toxin from Hansenula mrakii is known to inhibit cell wall beta-1,3-glucan synthase of Saccharomyces cerevisiae and other sensitive strains of yeast. A number of mutants of Saccharomyces cerevisiae that show resistance to this toxin were isolated in order to clarify the killing mechanism of the toxin. These mutants, designated rhk (resistant to Hansenula killer), were classified into three complementation groups. A novel gene RHK1, which complements the killer-resistant phenotype of the largest complementation group rhk1, was isolated. DNA sequence analysis revealed an open reading frame that encodes a hydrophobic protein composed of 458 amino acids. Gene disruption followed by tetrad analysis showed that RHK1 is not essential and loss of RHK1 function endowed S. cerevisiae cells with complete killer resistance. A biochemical analysis suggested that RHK1 does not participate directly in the synthesis of beta-1,3-glucan but is involved in the synthesis of the receptor for the HM-1 killer toxin.

Amino Acid Sequence↗

A new method for the assessment of venous insufficiency in primary varicose veins using near-infrared spectroscopy.

PURPOSE: Patients with chronic venous insufficiency (CVI) were evaluated from the aspect of ambulatory venous function using near-infrared spectroscopy (NIRS). METHODS: Seventy-two primary varicose veins of 59 patients (varicose group) and 20 normal limbs of 13 volunteers (normal group) were studied. The affected limbs of the patients were divided into three groups according to the classification advocated by an International Consensus Committee in 1995: mild CVI with class 2 or 3 (50 limbs); moderate CVI with class 4 (11 limbs); and severe CVI with class 5 or 6 (11 limbs). All of the patients underwent a treadmill walking test, during which NIRS was applied. Oxygenated hemoglobin (OxyHb) and deoxygenated hemoglobin (DeoHb) were continuously measured by NIRS during exercise. The ambulatory venous retention index (AVRI) obtained from serial changes in DeoHb was assessed comparatively in the four groups (normal and mild to severe CVI). In addition, 19 limbs in 13 patients were evaluated with air plethysmography for comparison with the data obtained by NIRS. RESULTS: Two distinct patterns of DeoHb change were observed. During exercise, the DeoHb level decreased in the normal group as a result of calf muscle contraction, whereas in the varicose group the DeoHb level rose because of an apparent venous reflux into the calf muscles. AVRI studies demonstrated a significant difference (p < 0.0001) among groups. Although there was no apparent relationship between AVRI and ejection fraction, AVRI showed a significant correlation with the venous filling index (r = 0.61) and a weak correlation with the residual volume fraction (r = 0.41). CONCLUSION: NIRS is useful for accurately assessing ambulatory venous dysfunction in patients with primary varicose veins.

Adult↗

Comparison of DNA copy numbers in original oral squamous cell carcinomas and corresponding cell lines by comparative genomic hybridization.

We analyzed regional DNA copy numbers in 4 oral squamous cell carcinomas (SCCs) by using comparative genomic hybridization, and compared them with those in cell lines derived from the SCCs. In the original tumors, DNA copy number increases were observed on chromosomes 5p (4/4 cases), 8q (4/4), 20p (3/4), 3q (2/4), 5q (2/4), 7p (2/4), 7q (2/4), 11p (2/4), 11q (2/4) and 13q (2/ 4). Although most of these changes have been described previously for SCC tumors in the head and neck, the incidence of increases in 8q and 20p was much higher in the present study; this may be important in relation to cell line establishment, since 8q contains e-myc, which is involved in immortalization. No common chromosomal region with DNA copy number decreases was observed, except for 18q (2/4). When the original tumors and the cell lines were compared, their profiles were essentially similar with one exception. Further, there was no region that commonly changed in the cell lines, but not in the original tumors, suggesting that the DNA copy number changes observed in the cell lines mostly represent those of the original tumors.

Adult↗

Cutaneous reflexes during human gait: electromyographic and kinematic responses to electrical stimulation.

The functions of ipsilateral cutaneous reflexes were studied with short trains of stimuli presented pseudorandomly to the superficial peroneal (SP) and tibial nerves during human gait. Electromyograms (EMGs) of tibialis anterior (TA), soleus, lateral and medial gastrocnemius, vastus lateralis (VL), and biceps femoris (BF) muscle were recorded, together with ankle and knee joint angles. Net reflex EMG responses were quantified in each of the 16 parts of the step cycle according to a recently developed technique. After SP nerve stimulation, TA muscle showed a significant suppression during swing phase that was highly correlated to ankle plantarflexion. BF and VL muscles were both excited throughout swing and significantly correlated to knee flexion during early swing. Tibial nerve stimulation caused dorsiflexion during late stance, but plantarflexion during late swing. We argue that SP nerve reflexes are indicative of a stumbling corrective response to nonnoxious electrical stimulation in humans. The correlated kinematic responses after tibial nerve stimulation may allow smooth movement of the swing leg so as to prevent tripping during swing and to assist placing and weight acceptance at the beginning of stance.

Adult↗