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Biomedical subjects

M Honda

Publications and source records attributed to M Honda.

At least 181 records · Page 10Linked to original sources

CAG repeat length in the androgen receptor gene is enhanced in patients with idiopathic azoospermia.

OBJECTIVES: To determine whether the number of CAG repeats in the androgen receptor gene is enhanced in patients with idiopathic azoospermia. METHODS: Using the polymerase chain reaction, the number of CAG repeats was assayed in 41 patients with idiopathic azoospermia and in 48 normozoospermic fertile men. RESULTS: In the control group, the CAG repeat length ranged from 17 to 30 (mean 23.9 +/- 2.9); in the azoospermic group, the CAG repeat length ranged from 20 to 34 (mean 26.5 +/- 3.5). The difference between the two groups was statistically significant (P = 0.0013). None of the men in the control group had a CAG repeat length greater than 31; four of the azoospermic men had 34 CAG repeats. CONCLUSIONS: Results suggest that an increase in the number of CAG repeats in the androgen receptor gene to 31 or greater may be associated with the etiology of at least some cases of idiopathic azoospermia.

Adenosine↗

Computer-assisted instructions for patients with bronchial asthma.

We produced computer-assisted instruction (CAI) software for bronchial asthma patients (asthma educational system with computer-assisted instruction; ASTCAI) to assist in self-management and avoid asthmatic attacks and death. ASTCAI is a question-and-answer program operating in a multimedia environment, and was evaluated from questionnaires which 33 patients were asked. Thirty-two patients could perform ASTCAI without any assistance. The responses of 31 patients (94%) indicated that they had no difficulty with manipulation, and 29 patients (88%) stated that the program was beneficial to control of their asthma. Elderly patients (over 65) required more time than younger adults. Emergency visits or admissions of at least 1 year after the first CAI trial decreased in eight out of 26 patients, while only two patients deteriorated compared to the previous year. Our results show that CAI is feasible for most patients, and through active self-learning CAI can improve motivation for self-management as well as supplement the physician's instructions.

Adolescent↗

Catharanthine oxidation in flavin mononucleotide-mediated catharanthine-vindoline coupling reaction for synthesis of dimeric indole alkaloids under near-ultraviolet light.

A reaction model for the flavin mononucleotide-mediated coupling of catharanthine (C) and vindoline (V) under near-ultraviolet light was established based on the results of experiments on the effects of various physical and chemical factors on the disappearance of C and V, and the synthesis of the product, a dihydropyridinium intermediate (IM). The following events were deduced to occur. (i) C is oxidized in the presence of FMN and oxygen under near-ultraviolet light (C(OX1)). (ii) C(OX1) then couples with V to form IM. Degradation of C occurs simultaneously with its specific oxidation, as a result of which a part of the C is converted into the product (C*) which is incapable of coupling with V. When a reaction in which C(OX1) is further oxidized to another form (C(OX2)) is added and the counterpart for the coupling with V is changed to C(OX2) from C(OX1), the reaction model more appropriately describes the exponential increase in the product, IM, that occurs in the early stage of the coupling reaction. (iii) The degradation rate of IM is much greater after C has been consumed than before its disappearance. Using this reaction model, the coupling reactions under basal and optimized conditions were simulated and the results showed a good fit with the experimental values under both conditions. The kinetic study suggests that manganese ion (Mn2+) stimulates the binding of C(OX2) with V in addition to suppressing the degradation of C, resulting in an increased yield of IM. Mn2+ thus appears to be an important factor in the coupling reaction, in which it plays two different roles.

Journal Article↗

Fuzziness of nonverbal courtship communication unblurred by motion energy detection.

A new method for the assessment of qualitative description of nonverbal behavior (automatic movie analysis) is introduced. This model-free method does not use any assumptions on the structure and organization of nonverbal behavior. Cross-cultural comparison (Germany, Japan) of unobtrusively filmed initial interactions between 2 opposite-sex strangers revealed no consistent courtship repertoire of directly observable behavior categories. Furthermore, an extensive analysis of gaze behavior and speech revealed differences between the countries but also showed no consistent relation to interest. Motion energy detection demonstrated in both cultures that female movement quality score (number of movements, duration, size, speed, and complexity) covaries with female interest. This effect is in concordance with the theory that in early stages of interactions manipulative efforts occur in order to avoid possible deception in high-risk situations.

Adolescent↗

Association of IL-6 gene alleles with systemic lupus erythematosus (SLE) and with elevated IL-6 expression.

To evaluate the association of alleles of regions having regulatory potential in the IL-6 gene, with SLE, the AT-rich minisatellite in the 3' flanking region and the 5' promoter-enhancer of the IL-6 gene were genotyped by PCR- and RFLP-based methods. The AT-rich minisatellite allele distribution pattern was significantly different in SLE (n = 146) as compared to 139 controls (chi 2(7) = 48.97, P = 0.001, Caucasians; and chi 2(7) = 19.93, P = 0.006, African-Americans). In either race, short allele sizes (< or = 792 bp) were seen exclusively in SLE patients (P = 0.001), whereas the 828-bp allele was over-represented in controls (P = 0.015 and 0.002). In contrast, there was no preferential association of SLE with G/C alleles in the 5' region of the IL-6 gene. Furthermore, our results suggest that the 3' minisatellite alleles have biological significance: (1) B lymphoblastoid cells of patients having one or two SLE-associated alleles secreted IL-6 in 3- to 4-fold higher levels than non-allelic cells (P < 0.05); (2) higher percentages (approximately 4-fold) of IL-6 positive monocytes were observed in individuals having SLE-associated IL-6 alleles; (3) in lupus patients having SLE-associated minisatellite alleles, IL-6 mRNA stability was significantly enhanced.

Adult↗

Gene-mutated HIV-1/SIV chimeric viruses as AIDS live attenuated vaccines for potential human use.

To develop an AIDS vaccine for human use as well as a suitable animal model for AIDS research, we constructed a series of HIV-1/SIVmac chimeric viruses (SHIVs). We successfully generated a SHIV (designated as NM-3rN) having the HIV-1 env gene, which enabled the evaluation of the efficacy of HIV-1 Env-targeted vaccines in macaque monkeys instead of chimpanzees. Two NM-3rN derivatives (NM-3 and NM-3n) induced long-term anti-virus immunities without manifesting the disease. The monkeys vaccinated with NM-3 or NM-3n became resistant to a challenge inoculation with NM-3rN. Serum from a monkey vaccinated with NM-3 neutralized not only the parental HIV-1 (NL432), but also an antigenically different HIV-1 (MN). In vivo experiments confirmed the heterologous protection against an SHIV having the HIV-1 (MN) env. In addition to specific immunity including neutralizing antibodies and cytotoxic T lymphocyte activity, nonspecific immunity such as natural killer activity is associated with this protection. These data suggest that the live vaccine has the ability to protect individuals against various types of HIVs. These SHIVs should contribute to the development of future anti-HIV-1 live vaccines in humans.

AIDS Vaccines↗

A search for a mutation in the tumour necrosis factor-alpha gene in narcolepsy.

The discovery of almost 100% association of narcolepsy with human leukocyte antigens (HLA) DR2 antigen prompted molecular biological research of this disorder. In the HLA class II gene cluster, the gene for tumour necrosis factor-alpha (TNF-alpha), which plays a role in the regulation of normal human sleep, is located. The present study searched for a mutation in the TNF-alpha gene by single-strand conformation polymorphism analysis (SSCP) in patients with narcolepsy. No mutation was detected in exons and introns of the TNF-alpha gene by SSCP and sequencing.

DNA Mutational Analysis↗

Novel intronic polymorphisms in the presenilin-2 gene and a case-control association study of Alzheimer's disease.

Several alleles of introns or untranslated regions in the presenilin-1 (PS-1) and presenilin-2 (PS-2) genes have been reported to behave as risk factors for senile Alzheimer's disease (AD). On the other hand, mutations in the three presenile AD genes also have been identified in a small number of sporadic presenile AD and senile AD cases. The present study evaluated the genetic contributions of PS-2 exons and introns to 56 senile and 18 Japanese cases of presenile AD using polymerase chain reaction single-strand conformation polymorphism analysis. In the PS-2 gene, one exonic polymorphic site without amino acid substitution, 9 intronic polymorphic sites, and 2 intronic variant sites were detected. However, in all cases, amino acid substitutions in exons between 4 and 12 of the PS-2 gene were not observed. The risk factors of senile and presenile AD were evaluated using a population-based study of restriction cleavages between patients and controls in introns 3, 4, 10 and 11. Regarding PS-2, there was no association between AD and intronic polymorphisms.

Alzheimer Disease↗

A PET study of sequential finger movements of varying length in patients with Parkinson's disease.

To study the difficulty that patients with Parkinson's disease have in performing long sequential movements, we used H2(15)O PET to assess the regional cerebral blood flow (rCBF) associated with the performance of simple repetitive movements, well-learned sequential finger movements of varying length and self-selected movements. Sequential finger movements in the Parkinson's disease patients were associated with an activation pattern similar to that found in normal subjects, but Parkinson's disease patients showed relative overactivity in the precuneus, premotor and parietal cortices. Increasing the complexity of movements resulted in increased rCBF in the premotor and parietal cortices of normal subjects; the Parkinson's disease patients showed greater increases in these same regions and had additional significant increases in the anterior supplementary motor area (SMA)/cingulate. Performance of self-selected movements induced significant activation of the anterior SMA/cingulate in normal subjects but not in Parkinson's disease patients. We conclude that in Parkinson's disease patients more cortical areas are recruited to perform sequential finger movements; this may be the result of increasing corticocortical activity to compensate for striatal dysfunction.

Adult↗

The role of the hippocampus in auditory processing studied by event-related electric potentials and magnetic fields in epilepsy patients before and after temporal lobectomy.

To clarify the relationship between the hippocampus and the event-related responses in auditory information processing, we recorded event-related potentials (ERPs) and event-related magnetic fields (ERFs) associated with the auditory oddball paradigm in 12 patients with temporal lobe epilepsy before and after surgical treatment, and in eight age-matched healthy volunteers. Lesions in the patients were hippocampal sclerosis (8), cyst (2), cavernoma (1) and calcified arteriovenous malformation (1), all in the unilateral temporal lobe. Standard temporal lobectomy (8), selective amygdalohippocampectomy (2), selective hippocampectomy (1) and inferior lateral temporal resection (1) were carried out. ERPs were recorded in nine patients before surgery, in all 12 patients after surgery, and in all normal subjects. P300 was maximal at Pz in the patients both before and after surgery, and in normal subjects. The peak latency and amplitude of P300 measured at Pz in the patients either before or after surgery did not differ significantly from those in normal subjects. After surgery, only the amplitude of P300 over the anterior and mid-temporal area on the resected side was attenuated, while it was symmetric before surgery regardless of the side of epileptogenic focus. ERFs were recorded in three patients before surgery and in six normal subjects by using a whole-head neuromagnetometer. ERFs in response to the target stimuli at a latency of approximately 400 ms were recognized at the anterior, middle and posterior lateral channels on each hemisphere (M400). The latency and dipole moments for M400 did not differ significantly between the patients before surgery and the normal subjects. As a result of analysis using the time-varying multidipole model, three dipoles for M400 were estimated in two patients in whom ERFs were available before surgery for the analysis, and in normal subjects: mesial temporal area, superior temporal area and inferior parietal area on each hemisphere. After surgery, in four out of six patients in whom ERFs were recordable, M400 at the anterior temporal channels on the resected side disappeared, and the activity in the affected mesial temporal area was lost. In one patient who underwent inferior lateral temporal resection, M400 waveforms and its sources were preserved in all regions. There were no significant differences in the latency and dipole moments of the unaffected source of M400 before versus after surgery. These results suggest that the hippocampus contributes to the scalp-recorded P300 only at the corresponding anterior temporal region, and does not influence its general waveform and predominant distribution over the scalp.

Adult↗

Mechanisms underlying gait disturbance in Parkinson's disease: a single photon emission computed tomography study.

Single photon emission computed tomography was used to evaluate regional cerebral blood flow changes during gait on a treadmill in 10 patients with Parkinson's disease and 10 age-matched controls. The subjects were injected with [99mTc]hexamethyl-propyleneamine oxime twice: while walking on the treadmill, which moved at a steady speed, and while lying on a bed with their eyes open. On the treadmill, all subjects walked at the same speed with their preferred stride length. The patients showed typical hypokinetic gait with higher cadence and smaller stride length than the controls. In the controls, a gait-induced increase in brain activity was observed in the medial and lateral premotor areas, primary sensorimotor areas, anterior cingulate contex, superior parietal cortex, visual cortex, dorsal brainstem, basal ganglia and cerebellum. The Parkinson's disease patients revealed relative underactivation in the left medial frontal area, right precuneus and left cerebellar hemisphere, whereas they showed relative overactivity in the left temporal cortex, right insula, left cingulate cortex and cerebellar vermis. This is the first experimental study showing that the dorsal brainstem, which corresponds to the brainstem locomotor region in experimental animals, is active during human bipedal gait. The reduced brain activity in the medial frontal motor areas is a basic abnormality in motor performance in Parkinson's disease. The underactivity in the left cerebellar hemisphere, in contrast to the overactivity in the vermis, could be associated with a loss of lateral gravity shift in parkinsonian gait.

Aged↗

A highly pathogenic simian/human immunodeficiency virus with genetic changes in cynomolgus monkey.

A highly pathogenic simian/human immunodeficiency virus (SHIV), designated C2/1, was obtained by serum passages in cynomolgus monkeys of p-SHIV, an SHIV strain that contains the env gene of pathogenic human immunodeficiency virus type 1 89.6. CD4+ lymphocyte depletion was induced within 1 week of the SHIV-C2/1 infection in peripheral blood as well as in various lymphoid organs in all the animals tested, with symptoms of diarrhoea and no increase in body weight, followed by intense viraemia. Serum antibody against Env protein was detected from 4 weeks after the virus infection, while the anti-Gag antibody response was absent in the SHIV-C2/1-infected animals. In contrast, both anti-Gag and anti-Env antibody responses were present in animals infected with p-SHIV or the non-pathogenic SHIV-MN. Sequencing of the env gene of isolates of SHIV-C strains showed conserved amino acid changes in the Env C2 and V3 regions that included changes to negatively charged amino acids, in the cytoplasmic region of gp41 that included a 42 amino acid deletion, and in the Nef protein. The pathogenic SHIV-C2/1-monkey model suggests that virus-specific pathogenicity in SHIV infection may be associated with the absence of anti-Gag antibody responses in animals and may be caused by genetic changes during serum passage in vivo.

Amino Acid Sequence↗

[Prevalence and serotypes of verocytotoxin-producing Escherichia coli (VTEC) isolates from dairy cattle].

To clarify the source of infection and route of transmission of Verocytotoxin-producing Escherichia coli (VTEC) in humans, we collected fresh feces from healthy dairy cattle reared in Hokkaido, Fukushima, Kanagawa and Okinawa prefectures between June 1996 and March 1997, and attempted to isolate VTEC. The results are described below. 1) VTEC was isolated from 68 (27.1%) of 251 fecal samples tested. VTEC was isolated from 14 (28.0%) of 50 in Hokkaido, 13 (26.0%) of 50 in Fukushima, 20 (39.2%) of 51 in Kanagawa and 21 (21.0%) of 100 in Okinawa. There were no difference in the prevalence among the prefectures. 2) Toxin type and serotype of 85 isolates were determined. Thirty-three isolaties (38.8%) were classified into VT1 toxin and VT2 toxin, respectively, and 19 isolates (22.4%) were classified as the strain that produces both VT1 and VT2 toxins. The toxin types of these isolates were divided by serotypes. The VT1-producing isolates were the most frequent among O111:H-. The VT2-producing isolates included O2:H12, O2:H29, O2:H-, O82:H8, O82:HUT, O153:H19, O153:H42 and O153:H-. Among the isolates producing both VT1 and VT2 toxins, O153:H19 was relatively frequent. Based on findings that many bacterial strains coinciding with toxin types and serotypes of human-derived VTEC isolated from dairy cattle, it was suggested that dairy cattle are closely related to VTEC infection in human as a source of infection.

Animals↗

Cyclic-imide-hydrolyzing activity of D-hydantoinase from Blastobacter sp. strain A17p-4.

The cyclic-imide-hydrolyzing activity of a prokaryotic cyclic-ureide-hydrolyzing enzyme, D-hydantoinase, was investigated. The enzyme hydrolyzed cyclic imides with bulky substituents such as 2-methylsuccinimide, 2-phenylsuccinimide, phthalimide, and 3,4-pyridine dicarboximide to the corresponding half-amides. However, simple cyclic imides without substituents, which are substrates of imidase (ie.g., succinimide, glutarimide, and sulfur-containing cyclic imides such as 2,4-thiazolidinedione and rhodanine), were not hydrolyzed. The combined catalytic actions of bacterial D-hydantoinase and imidase can cover the function of a single mammalian enzyme, dihydropyrimidinase. Prokaryotic D-hydantoinase also catalyzed the dehyrative cyclization of the half-amide phthalamidic acid to the corresponding cyclic imide, phthalimide. The reversible hydrolysis of cyclic imides shown by prokaryotic D-hydantoinase suggested that, in addition to pyrimidine metabolism, it may also function in cyclic-imide metabolism.

Amidohydrolases↗

A phylogenetically conserved stem-loop structure at the 5' border of the internal ribosome entry site of hepatitis C virus is required for cap-independent viral translation.

Hepatitis C virus (HCV) initiates translation of its polyprotein under the control of an internal ribosome entry site (IRES) that comprises most of the 341-nucleotide (nt) 5' nontranslated RNA (5'NTR). A comparative analysis of related flaviviral sequences suggested that an RNA segment for which secondary structure was previously ill defined (domain II, nt 44 to 118) forms a conserved stem-loop that is located at the 5' border of the HCV IRES and thus may function in viral translation. This prediction was tested by a mutational analysis of putative helical structures that examined the impact of both covariant and noncovariant nucleotide substitutions on IRES activity in vivo and in vitro. Results of these experiments provide support for predicted base pair interactions between nt 44 to 52 and 111 to 118 and between nt 65 to 70 and 97 to 102 of the HCV 5'NTR. Substitutions at either nt 45 and 46 or nt 116 and 117 resulted in reciprocal changes in V1 nuclease cleavage patterns within the opposing strand of the putative helix, consistent with the predicted base pair interactions. IRES activity was highly dependent on maintenance of the stem-loop II structure but relatively tolerant of covariant nucleotide substitutions within predicted helical segments. Sequence alignments suggested that the deduced domain II structure is conserved within the IRESs of pestiviruses as well as the novel flavivirus GB virus B. Despite marked differences in primary nucleotide sequence within conserved helical segments, the sequences of the intervening single-stranded loop segments are highly conserved in these different viruses. This suggests that these segments of the viral RNA may interact with elements of the host translational machinery that are broadly conserved among different mammalian species.

5' Untranslated Regions↗

Natural variation in translational activities of the 5' nontranslated RNAs of hepatitis C virus genotypes 1a and 1b: evidence for a long-range RNA-RNA interaction outside of the internal ribosomal entry site.

The 5' nontranslated RNA (5'NTR) of a genotype 1b hepatitis C virus (HCV-N) directs cap-independent translation of the HCV-N polyprotein with about twofold less efficiency than the 5'NTR of a genotype 1a virus under physiologic conditions (Hutchinson strain, or HCV-H) (M. Honda et al., Virology 222:31-42, 1996). Here, we show by mutational analysis that substitution of the AG dinucleotide sequence at nucleotides (nt) 34 and 35 of HCV-N with GA (present in HCV-H) restores the translational activity to that of the HCV-H 5'NTR both in vitro and in vivo. These nucleotides are located upstream of the minimal essential internal ribosome entry site (IRES), as a 6-nt deletion spanning nt 32 to 37 also increased the translational activity of the HCV-N 5'NTR to that of HCV-H. Thus, the upstream AG dinucleotide sequence has an inhibitory effect on IRES-directed translation. Surprisingly, however, this inhibitory effect was observed only when the translated, downstream RNA sequence contained nt 408 to 929 of HCV (capsid-coding RNA). Further analysis of RNA transcripts containing frameshift mutations demonstrated that the nucleotide sequence of the transcript, and not the amino acid sequence of the expressed capsid protein, determines this difference in translation efficiency. The difference between the translational activities of the HCV-N and HCV-H transcripts was increased when translation was carried out in reticulocyte lysates containing high K+ concentrations, with a sevenfold difference evident at 130 to 150 mM K+. These results suggest that there is an RNA-RNA interaction involving 5'NTR and capsid-coding sequences flanking the IRES and that this is responsible for the reduced IRES activity of the genotype 1b virus, HCV-N.

5' Untranslated Regions↗

Mesial motor areas in self-initiated versus externally triggered movements examined with fMRI: effect of movement type and rate.

The human frontomesial cortex reportedly contains at least four cortical areas that are involved in motor control: the anterior supplementary motor area (pre-SMA), the posterior SMA (SMA proper, or SMA), and, in the anterior cingulate cortex, the rostral cingulate zone (RCZ) and the caudal cingulate zone (CCZ). We used functional magnetic resonance imaging (fMRI) to examine the role of each of these mesial motor areas in self-initiated and visually triggered movements. Healthy subjects performed self-initiated movements of the right fingers (self-initiated task, SI). Each movement elicited a visual signal that was recorded. The recorded sequence of visual signals was played back, and the subjects moved the right fingers in response to each signal (visually triggered task, VT). There were two types of movements: repetitive (FIXED) or sequential (SEQUENCE), performed at two different rates: SLOW or FAST. The four regions of interest (pre-SMA, SMA, RCZ, CCZ) were traced on a high-resolution MRI of each subject's brain. Descriptive analysis, consisting of individual assessment of significant activation, revealed a bilateral activation in the four mesial structures for all movement conditions, but SI movements were more efficient than VT movements. The more complex and more rapid the movements, the smaller the difference in activation efficiency between the SI and the VT tasks, which indicated an additional processing role of the mesial motor areas involving both the type and rate of movements. Quantitative analysis was performed on the spatial extent of the area activated and the percentage of change in signal amplitude. In the pre-SMA, activation was more extensive for SI than for VT movements, and for fast than for slow movements; the extent of activation was larger in the ipsilateral pre-SMA. In the SMA, the difference was not significant in the extent and magnitude of activation between SI and VT movements, but activation was more extensive for sequential than for fixed movements. In the RCZ and CCZ, both the extent and magnitude of activation were larger for SI than for VT movements. In the CCZ, both indices of activation were also larger for sequential than for fixed movements, and for fast than for slow movements. These data suggest functional specificities of the frontomesial motor areas with respect not only to the mode of movement initiation (self-initiated or externally triggered) but also to the movement type and rate.

Adult↗