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Biomedical subjects

H Sekiya

Publications and source records attributed to H Sekiya.

At least 19 recordsLinked to original sources

[General anesthesia in a patient with Cornelia de Lange syndrome with restricted opening of the mouth].

Patients with Cornelia de Lange syndrome have many anomalies including micrognathia with a small mouth, a high arched palate, and a short neck, which might make laryngoscopy for tracheal intubation difficult during induction of general anesthesia. General anesthesia was performed in a patient with Cornelia de Lange syndrome, and restricted opening of the mouth, which had not been reported previously, was found during laryngoscopy. The possible causes were thought to be temporo-mandibular joint disorders, contracture of the masseter muscle due to injury by self-destructive tendencies, or elogated coronoid process. The potential difficulty with laryngoscopy should be considered for tracheal intubation in a patient with Cornelia de Lange syndrome.

Adult

The contextual interference effect in parameter modifications of the same generalized motor program.

This study extended previous work (Sekiya, Magill, Sidaway, & Anderson, 1994) by examining whether the contextual interference (CI) effect could be found when task variations were controlled by the same generalized motor program (GMP) but differentiated on the basis of overall force parameter modifications. A subsidiary aim of this study was to determine how the amount of practice influenced the CI effect. During 2 acquisition sessions and 2 retention sessions, participants (N = 24) performed 3 task variations in either a blocked (low CI) or serial (high CI) condition. The task variations shared the same relative force structures but differed in the amount of overall force that had to be produced. Analysis of a general error measure revealed a strong CI effect, indicating that overall force parameter modifications of the same GMP created the CI effect. Analyses of various dependent measures, which dissociated GMP from parameter components with regard to force characteristics, revealed that parameter learning, but not GMP learning, was enhanced by high CI practice. No CI effect occurred in any aspect of timing characteristics. The amount of practice used in the present study did not influence the efficacy of the CI effect.

Adult

The motoneurons innervating the musculus levator palpebrae superiors in the monkey, cat and rabbit.

The motoneurons innervating the musculus levator palpebrae superioris (LPS) of the monkey, the cat and the rabbit were studied using horseradish peroxidase (HRP). Furthermore, LPS motoneurons of the cat and rabbit were studied by the double-labeling method using two fluorescent dyes as retrograde neuronal tracers. After injection of HRP into the right LPS of the monkey and the cat, HRP-labeled neurons were found only in the central caudal nucleus with contralateral preponderance. In contrast, after HRP injection into the right LPS of the rabbit, HRP-labeled neurons were found only in the contralateral oculomotor nucleus. In the double-labeling study, after injection of fast blue (FB) into the right LPS and diamidino yellow dihydrochloride (DY) into the left LPS of the cat and the rabbit, no double-labeled neurons were noted in the central caudal nucleus of the cat nor in the oculomotor nucleus of the rabbit, although double-labeled neurons were identified in the central caudal nucleus of the monkey in our previous study. Cross-innervation was confirmed in the mammals lower than the monkey.

Amidines

Genetic alterations of the putative envelope proteins encoding region of the hepatitis C virus in the progression to relapsed phase from acute hepatitis: humoral immune response to hypervariable region 1.

Hypervariable region I (HVRI) of the putative second envelope glycoprotein (gp70) of hepatitis C virus (HCV) undergoes sequential alterations at intervals of several months during the chronic phase of hepatitis. To evaluate the implications of sequence variability in HVRI of HCV, we investigated the sequence variability of the whole envelope-protein(gp35 and gp70)-coding regions of HCV genome derived from patient M in acute and relapsed phases (8-month interval) of hepatitis. From this analysis, we found that a Leu (position 405) in HVRI substituted to Pro, and that 4 additional substitutions could be detected in gp70 during the relapsed phase. Sequence-specific antibody against HVRI derived from patient M was first detected in the serum at 8 months after the onset of hepatitis, but no other specific antibodies against peptides containing amino-acid position(s) substituted in regions other than HVRI could be detected. Epitope mapping using the sequence of HVRI derived from the acute phase of hepatitis was also performed, and a B-cell epitope (positions 397 to 407) of 11 amino acids was identified. However, the Pro variant at position 405 did not display an escape pattern from the antibody produced at 8 months after the onset. In addition, we demonstrated the existence of important amino-acid residue positions which are recognized by the anti-HVRI antibody produced in patient M using introduction point mutations within HVRI.

Adult

Genetic alteration of the hepatitis C virus hypervariable region obtained from an asymptomatic carrier.

Hepatitis C virus (HCV) genome shows extensive sequence diversity at 2 hypervariable regions (HVR1 and HVR2) of the putative envelope glycoprotein (gp70). We recently reported that the amino-acid sequence of HVR1, but not of HVR2, underwent a striking mutation or mutated sequentially over a period of several months in patients with chronic hepatitis (CH). Here, we examined whether these genetic alterations in HVR1 occurred in an asymptomatic HCV carrier. The level of HCV RNA in serum was almost the same throughout the 4 time points sampled over 16 months. However, we found that the amino-acid sequence of the HCV HVR1 from this asymptomatic carrier altered with time, as seen in patients with CH. Alterations of amino acids in the HVR1 were correlated with persistent HCV infection rather than with clinical symptoms. Sequence heterogeneity of HVR1 was not correlated with alanine aminotransferase (ALT) values or liver histological findings. The necessity of clinical follow-up of HCV asymptomatic carriers is discussed.

Adult

The contextual interference effect for skill variations from the same and different generalized motor programs.

Magill and Hall (1990) hypothesized that the contextual interference (CI) effect is found only when task variations to be learned are governed by different generalized motor programs (GMPs). The present experiments examined their hypothesis by requiring subjects to learn variations of a tapping task that had either different (Experiment 1) or the same (Experiment 2) relative timing structure. In each experiment, subjects (N = 36) performed 270 acquisition trials with knowledge of results (KR) in either a blocked or a serial order. One day later, subjects performed 30 retention trials without KR. In data analyses, errors due to parameter modifications were dissociated from errors due to GMP construction to examine which process was responsible for the CI effect. In both experiments, parameter learning created a CI effect while GMP learning failed to produce a CI effect. In the light of these findings, a modification is proposed to the Magill and Hall (1990) hypothesis that takes into account these distinct processes in motor learning.

Adult

Genetic drift in hypervariable region 1 of the viral genome in persistent hepatitis C virus infection.

The hypervariable region 1 (HVR1) of the putative second envelope glycoprotein (gp70) of hepatitis C virus (HCV) contains a sequence-specific immunological B-cell epitope that induces the production of antibodies restricted to the specific viral isolate, and anti-HVR1 antibodies are involved in the genetic drift of HVR1 driven by immunoselection (N. Kato, H. Sekiya, Y. Ootsuyama, T. Nakazawa, M. Hijikata, S. Ohkoshi, and K. Shimotohno, J. Virol. 67:3923-3930, 1993). We further investigated the sequence variability of the HCV genomic region that entirely encodes the envelope proteins (gp35 and gp70); these sequences were derived from virus isolated during the acute and chronic phases of hepatitis in one patient, and we found that HVR1 was a major site for genetic mutations in HCV after the onset of hepatitis. We carried out epitope-mapping experiments using the HVR1 sequence derived from the acute phase of hepatitis and identified two overlapping epitopes which are each composed of 11 amino acids (positions 394 to 404 and 397 to 407). The presence of two epitopes within HVR1 suggested that epitope shift happened during the course of hepatitis. Four of six amino acid substitutions detected in HVR1 were located within the two epitopes. We further examined the reactivities of anti-HVR1 antibodies to the substituted amino acid sequences within the two epitopes. HVR1 variants in both epitopes within the HVR1 escaped from anti-HVR1 antibodies that were preexisting in the patient's serum.

Adult

Sensitivity of nasal and temporal hemiretinas in latent nystagmus and strabismus evaluated using the light reflex.

To determine visual sensitivity in patients with latent nystagmus with or without esotropia or exotropia, and in patients with esotropia or exotropia, pupillary reactions to 5 degrees diameter light stimuli given to the retina at the fovea (centre), at 5 degrees nasal to the centre, and at 5 degrees temporal to the centre, were measured using electronic infrared pupillography; then pupillary constriction rates and maximum velocity of pupillary constrictions were calculated and analysed. In non-dominant eyes, visual sensitivities of the nasal retina and temporal retina were higher compared with normal eyes, and they also tended to be higher than the sensitivities at the fovea (centre), particularly in patients with latent nystagmus with esotropia. In patients with esotropia or exotropia, visual sensitivities in non-dominant eyes of the nasal retina, and temporal retina increased to a level similar to those at the fovea (centre). The magnitude of these abnormalities was greater in patients with latent nystagmus with esotropia, those with latent nystagmus, and those with latent nystagmus with exotropia, esotropia, and exotropia, in that order. From these results, it was assumed that this imbalance is transmitted to the motor system, resulting in the onset of latent nystagmus.

Adolescent

Possible role of preS2 peptides presented by MHC class I antigen in the pathogenesis of chronic hepatitis B.

Many variations exist in the first 39 nucleotides of the preS2 (pre-S2; 1-39) region of the HBV genome. Based on the similarities of their coding amino acid sequences to those of prototype HBV, they were classified into 3 different types, adr-preS2, adw-preS2 and ayw-preS2. To clarify the meaning of these variabilities in the preS2 region, we studied the HLA class I phenotype of chronic hepatitis B patients having high levels of serum ALT. Our results indicated that in 12 of 14 chronic hepatitis patients infected with HBV type adr-preS2 had HLA-A24 phenotype whereas all of 7 patients infected with either adw- or ayw-preS2 HBV had HLA-A2 phenotype. This strong association between HLA class I phenotype and certain preS2 types of HBV infection was found only in patients with high serum ALT levels but not in patients with almost normal levels of serum ALT. Our results therefore suggest that in the generation of chronic hepatitis B a suitable combination between a fragment of preS2 antigen and HLA class I antigens of the infected host, such as adr-preS2 with HLA-A24 and either adw- or ayw-preS2 with HLA-A2, might be required.

Base Sequence

Humoral immune response to hypervariable region 1 of the putative envelope glycoprotein (gp70) of hepatitis C virus.

We recently found that alterations of amino acids in hypervariable region 1 (HVR1) of the putative envelope glycoprotein (gp70) of hepatitis C virus (HCV) occurred sequentially in the chronic phase of hepatitis at intervals of several months. This finding suggests that mutations in HVR1 are involved in the mechanism of persistent chronic HCV infection involving escape from the immunosurveillance system. To explore this possibility, we examined the humoral immune response to HVR1 with our assay system, in which immunoprecipitation was carried out with sera from patients by using an HVR1 (27-amino-acid) dihydrofolate reductase fusion protein synthesized by in vitro transcription and translation. Results showed that HVR1 contains a sequence-specific immunological epitope that induces the production of antibodies restricted to the specific viral isolate. Furthermore, analysis of the kinetics of the appearance of antibodies in two patients with chronic hepatitis, with whom successive alterations of amino acids of HVR1 have been observed, showed that the titers of anti-HVR1 antibodies usually reached maximal levels several months after the isolation of HCV having the specific sequence of HVR1. This observation suggests that anti-HVR1 antibodies are involved in the genetic drift of HVR1 (minor antigenic variation) by immunoselection. However, the coexistence of HVR1 as an antigen and its specific antibody was sometimes observed. The possibility that HVR1 acts as a neutralizing epitope is discussed.

Adult

[The effect of organophosphorus pesticide (fenthion) on GABA-cells in the central nuclei].

Organophosphorus pesticide (OP) produces abnormal eye movements. This is possibly due to an inhibition of central cholinergic neurons as well as GABAnergic neurons. Using anti-GABA-antibody, the authors studied the effect of OP on GABA-positive cells in the central nervous system. Fenthion (dimethyl 4-methylthion-m-tolyl-phosphorothionate, 20 mg/kg body weight), was given subcutaneously to the dorsal portion of Wistar rats for 30 days. After staining, the number of GABA-positive cells were counted at the superior colliculus (SC), the cerebellum, and the substantia nigra reticularis (SNR) on day 6, 10, 14, 18, 22, 26 and 30 respectively. The number of GABA-positive cells reduced in the cerebellum, SNR and SC decreasing remarkably after the initiation of fenthion administration. The number of GABA-positive cells also decreased in lateral geniculate nucleus and pretectal nuclei. Those results suggest that the reduction of GABA-positive cells produces abnormal eye movements in human OP intoxication.

Animals

Characterization of hypervariable regions in the putative envelope protein of hepatitis C virus.

We previously identified two hypervariable regions [HVR1 (27 amino acids) and HVR2 (7 amino acids)] in the putative envelope glycoprotein (gp70) by comparison of the amino acid sequences of many isolates of the HCV-II genotype. To understand the functional features of these HVRs, using the polymerase chain reaction we analyzed the rate of actual sequence variability in the region including HVR1 and HVR2 of HCV isolated successively at intervals of several months from two patients with chronic C-type hepatitis. In both patients, the amino acid sequence of HVR1, but not HVR2, was found to change dramatically during the observation period (about one amino acid per month). However, no alteration of the amino acid sequence of HVR1 of HCV was observed in a patient in the acute phase of chronic hepatitis. Restriction digestion analysis of sequence diversity showed that a HCV genome with a newly introduced mutation in HVR1 often became the predominant population at the next time of examination. Alterations of amino acids in HVR1 occurred sequentially in the two patients in the chronic phase. These findings suggest that mutations in HVR1 are involved in the mechanism of persistent chronic HCV infection.

Alanine Transaminase

Bilateral innervation of the musculus levator palpebrae superioris by single motoneurons in the monkey.

The location of motoneurons innervating the musculus levator palpebrae superioris (LPS) was studied in the monkey (Macaca irus) by using Fast blue (FB) and propidium iodide (PI) as retrograde neuronal tracers. In each monkey, FB was injected into the LPS of one eye and PI into the LPS of the other eye. Neuronal cell bodies labeled with FB and/or PI were seen intermixed bilaterally through the entire rostrocaudal extent of the central caudal nucleus. While single-labeled (70%) cell bodies predominated, many double-labeled (30%) cell bodies were also encountered. Each of the double-labeled neurons was concluded to supply the LPS on both sides by way of axon collaterals.

Animals

[Free synovium grafting for the repair of the avascular portion of canine knee joint meniscus].

To evaluate the effect of free synovium on repair of avascular portion of the meniscus in the knee, two round full-thickness defects of 2 mm phi were made in the medial menisci of 57 dogs, followed by transplantation of free synovium or blood clots in the holes. Defects with no grafting served as control. Specimens were evaluated histologically at intervals from 1 day to 12 weeks after grafting. The portions of the medial menisci filled with blood clots gradually retracted after surgery and showed no complete repair 6 and 12 weeks after the operation as in the control. In the group which received synovial graft, however, fibrous reparation was observed in 62% of total 13 defects 3 weeks after grafting. Six and 12 weeks after the synovial transplantation, complete reparation by fibrocartilaginous tissue with no signs of tissue retraction was observed in more than 65% of total 17 defects. Therefore, synovial grafting seemed to be a potential method for the repair of the avascular portion of the canine knee joint meniscus.

Animals

[Localization of motoneurons of the vertical yoke muscles in a brainstem of the cat--a double labeling study].

Motor neurons innervating the vertical yoke muscles in cats were investigated using fluorescent dyes by the double labeling method. In 4 cats, the right superior rectus muscle (SR) and left inferior oblique muscle (IO) were injected with 3% fast blue (FB) and 5% diamidino yellow dihydrochloride (DY), respectively, for observing motoneurons innervating yoke muscles involving upward gaze. In 4 other cats, the left inferior rectus muscle (IR) and right superior oblique muscle (SO) were injected with 3% FB and 5% DY, respectively, to observe motoneurons innervating yoke muscles involving downward gaze. After SR and SO injections labeled cells were found in the bilateral oculomotor nucleus and the bilateral trochlear nucleus, respectively, predominantly on the contralateral side. Following IR and IO injections labeled cells were found only in the ipsilateral oculomotor nucleus. No double labeled cell was observed in any labeled neurons, which indicates that each of the yoke muscles was innervated by independent individual motoneurons. According to the present observation and past reports on rats, cats and monkeys, motoneurons innervating SR and SO have developed from lower mammals such as the rat into predominantly contralateral innervation in the monkey, from a phylogenetic point of view. On the other hand, compared to contralateral innervation in lower mammals, motoneurons innervating IR and IO have developed into ipsilateral innervation in the monkey.

Amidines

The center for controlling the near reflex in the midbrain of the monkey: a double labelling study.

The center for controlling the near reflex was studied in the midbrain of the monkey using Diamidino yellow dihydrochloride (DY) and Fast blue (FB) as retrograde neuronal tracers. After injection of DY into the ciliary ganglion, many labelled neurons were found ipsilaterally in the anteromedian nucleus, the Edinger-Westphal nucleus, and the nucleus of Perlia. In contrast, after injection of FB into the medial rectus muscle, labelled cells were found ipsilaterally only in the Edinger-Westphal nucleus of the visceral nuclei as well as in the somatic ipsilateral nuclei. No double labelling of cells was noted in the Edinger-Westphal nucleus, establishing the premise that FB-labelled cells were subserving medial rectus muscle and pupillary/accommodative functions and DY cells were subserving pupillary/accommodative functions independently.

Amidines