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Biomedical subjects

Ken Inoue

Publications and source records attributed to Ken Inoue.

At least 19 recordsLinked to original sources

The correlation between unemployment and suicide rates in Japan between 1978 and 2004.

The number of suicides in Japan has increased from approximately 22,000 per year from 1988 to 1997 to over 30,000 per year since then; this increase is among the most important problems facing Japan. Moreover, the unemployment rate in Japan has increased rapidly since 1998. In this study, we examined the total number of suicides and both the suicide and unemployment rates in Japan from 1978 to 2004. We also focused on the correlation between annual suicide rates in Japan and the annual unemployment rates during the study period. During that period, 455,357 males and 225,012 females committed suicide in Japan, and the suicide rates by sex were 27.8 males and 13.3 females per 100,000 population (P<0.05). The annual suicide rates among males correlated significantly with the annual unemployment rates: r(27)=0.94, P<0.001, while the female suicide rates did not correlate with the unemployment rates: r(27)=0.39, P=0.05. Thus, when unemployed men are observed to be depressed, it is important for those close to them, as well as their health care professionals, to pay careful attention to their behavior to detect suicidal tendencies or intentions.

Female↗

Suicidal tendencies among the elderly in Mie Prefecture, Japan, between 1996 and 2002.

This study aims to show the causative factors of suicide among the elderly (over 65) in Mie Prefecture, and to discuss the prevention of the factors contributing to suicide in the elderly group. We obtained an agreement from the Mie Prefectural Police Headquarters and investigated all inquest records collected between 1996 and 2002 in Mie Prefecture and focused on suicide in the elderly group. During the test period, the number of suicides in the elderly group was 842. In causative factors, the two major causative factors of suicide were "suffering from physical illness" and "psychiatric disorders". In particular, the three most frequent physical illnesses were "cardiovascular disease", "orthopedic disorder", and "digestive organ disease", and these physical illnesses are mentally stressful, and thus have a psychiatric component, the same as psychiatric illnesses do. Consequently, it is concluded that improvements in the home nursing and mental health care should include the prevention of suicide in the elderly who "suffer from physical illness" and "psychiatric disorders" to prevent suicide. In addition, medical staff and the general public should be educated on the factors that can influence elderly persons' mental condition, and should be cautioned to observe elderly persons for suicidal signs and symptoms.

Adult↗

A case of human fasciolosis: discrepancy between egg size and genotype of Fasciola sp.

In human fasciolosis, differential diagnosis of the causative flukes, Fasciola hepatica and Fasciola gigantica, is problematic. We report a rare case of human fasciolosis in which an adult worm was recovered from the bile duct of a Japanese man. Morphometric data of the worm were consistent with those of F. hepatica, whereas the size of eggs in the stool indicated infection with F. gigantica. Nucleotide sequences of ITS-1 and -2 and CO1 genes of the DNA extracted from the eggs revealed that the genotype was that of F. hepatica. These findings suggest that the size of eggs is not a suitable marker for species identification in human fasciolosis, especially in settings such as the East Asian region where different karyotypes and hybrid genotypes of F. hepatica and F. gigantica have been found.

Aged↗

Role of genomic architecture in PLP1 duplication causing Pelizaeus-Merzbacher disease.

Genomic architecture, higher order structural features of the human genome, can provide molecular substrates for recurrent sub-microscopic chromosomal rearrangements, or may result in genomic instability by forming structures susceptible to DNA double-strand breaks. Pelizaeus-Merzbacher disease (PMD) is a genomic disorder most commonly arising from genomic duplications of the dosage-sensitive proteolipid protein gene (PLP1). Unlike many other genomic disorders that result from non-allelic homologous recombination utilizing flanking low-copy repeats (LCRs) as substrates, generating a common and recurrent rearrangement, the breakpoints of PLP1 duplications have been reported not to cluster, yielding duplicated genomic segments of varying lengths. This suggests a distinct molecular mechanism underlying PLP1 duplication events. To determine whether structural features of the genome also facilitate PLP1 duplication events, we analyzed extensively the genomic architecture of the PLP1 region and defined several novel LCRs (LCR-PMDs). Array comparative genomic hybridization showed that PLP1 duplication sizes differed, but revealed a subgroup of patients with apparently similar PLP1 duplication breakpoints. Pulsed-field gel electrophoresis analysis using probes adjacent to the LCR-PMDs detected unique recombination-specific junction fragments in 12 patients, enabled us to associate the LCR-PMDs with breakpoint regions, and revealed rearrangements inconsistent with simple tandem duplications in four patients. Two-color fluorescence in situ hybridization was consistent with directly oriented duplications. Our study provides evidence that PLP1 duplication events may be stimulated by LCRs, possibly non-homologous pairs at both the proximal and distal breakpoints in some cases, and further supports an alternative role of genomic architecture in rearrangements responsible for genomic disorders.

Base Sequence↗

Nonsense-mediated mRNA decay modulates clinical outcome of genetic disease.

The nonsense-mediated decay (NMD) pathway is an mRNA surveillance system that typically degrades transcripts containing premature termination codons (PTCs) in order to prevent translation of unnecessary or aberrant transcripts. Failure to eliminate these mRNAs with PTCs may result in the synthesis of abnormal proteins that can be toxic to cells through dominant-negative or gain-of-function effects. Recent studies have expanded our understanding of the mechanism by which nonsense transcripts are recognized and targeted for decay. Here, we review the physiological role of this surveillance pathway, its implications for human diseases, and why knowledge of NMD is important to an understanding of genotype-phenotype correlations in various genetic disorders.

Alleles↗

Possible neuroleptic malignant syndrome related to concomitant treatment with paroxetine and alprazolam.

A 74-year-old man with depressive symptoms was admitted to a psychiatric hospital due to insomnia, loss of appetite, exhaustion, and agitation. Medical treatment was initiated at a daily dose of 20 mg paroxetine and 1.2 mg alprazolam. On the 10th day of paroxetine and alprazolam treatment, the patient exhibited marked psychomotor retardation, disorientation, and severe muscle rigidity with tremors. The patient had a fever (38.2 degrees C), fluctuating blood pressure (between 165/90 and 130/70 mg mm Hg), and severe extrapyramidal symptoms. Laboratory tests showed an elevation of creatine phosphokinase (2218 IU/L), aspartate aminotransferase (134 IU/L), alanine aminotransferase (78 IU/L), and BUN (27.9 mg/ml) levels. The patient received bromocriptine and diazepam to treat his symptoms. 7 days later, the fever disappeared and the patient's serum CPK levels were normalized (175 IU/L). This patient presented with symptoms of neuroleptic malignant syndrome (NMS), thus demonstrating that NMS-like symptoms can occur after combined paroxetine and alprazolam treatment. The adverse drug reaction score obtained by the Naranjo algorithm was 6 in our case, indicating a probable relationship between the patient's NMS-like adverse symptoms and the combined treatment used in this case. The involvement of physiologic and environmental aspects specific to this patient was suspected. Several risk factors for NMS should be noted in elderly depressive patients whose symptoms often include dehydration, agitation, malnutrition, and exhaustion. Careful therapeutic intervention is necessary in cases involving elderly patients who suffer from depression.

Aged↗

Spastic paraplegia type 2 associated with axonal neuropathy and apparent PLP1 position effect.

OBJECTIVE: To report an association between spastic paraplegia type 2 with axonal peripheral neuropathy and apparent proteolipid protein gene (PLP1) silencing in a family. METHODS: Pulsed-field gel electrophoresis, custom array comparative genomic hybridization, and semi-quantitative multiplex polymerase chain reaction analyses were used to examine the PLP1 genomic region. RESULTS: Electrodiagnostic studies and a sural nerve biopsy showed features of a dystrophic axonal neuropathy. Molecular studies identified a small duplication downstream of PLP1. INTERPRETATION: We propose the duplication to result in PLP1 gene silencing by virtue of a position effect. Our observations suggest that genomic rearrangements that do not include PLP1 coding sequences should be considered as yet another potential mutational mechanism underlying PLP1-related dysmyelinating disorders.

DNA Mutational Analysis↗

Sensitivity to seasonal changes in panic disorder patients.

It has been suggested that symptoms of panic disorder may be significantly affected by seasonal factors including weather changes, although few studies have explored the issue. The purpose of the present paper was to investigate clinical data to examine sensitivity of panic disorder patients to seasonal changes and seasonal fluctuation of panic disorder symptoms. A self-rating questionnaire consisting of the Seasonal Pattern Assessment Questionnaire (SPAQ) and additional self-rating questions were analyzed in 146 Japanese patients (50 male, 96 female) with panic disorder (DSM-IV) at an outpatient clinic for anxiety disorder. The average of the Global Seasonality Scores (GSS) was 12.5+/-4.7 and 25.3% of the patients were suggested to suffer from seasonal affective disorder, according to the GSS. Frequency of the panic attack was found to fluctuate seasonally, with peaks in August and December (P=0.005 and 0.01, chi2 test). The present results indicate that panic disorder patients may be more sensitive to seasonal and meteorological factors than the general population and become more fragile in a specific season or months. This might assist in the development of preventive measures for the frequent recurrence of symptoms in panic disorder.

Adult↗

Causative factors as cues for addressing the rapid increase in suicide in Mie Prefecture, Japan: comparison of trends between 1996-2002 and 1989-1995.

The number of suicides in Japan has increased from approximately 22 000 per year from 1988 to 1997 to >30 000 per year since 1998. Likewise, the number of suicides has been increasing in Mie Prefecture. The purpose of the present study was to examine the incidence of and circumstances surrounding all suicide cases during 1996-2002 in Mie Prefecture and to compare the data with those from 1989 to 1995. In Mie Prefecture, the age-specific suicide rate during the second 7-year period included marked increases among men aged 50-59 and 60-69 years. Among women, the age-specific suicide rate increased with age during both 7-year periods. During the second period, psychiatric disorders as causative factors increased in all generations. They were especially important for women of the younger generation, whereas economic problems were the most common causative factor among men aged 40-64. Physical illness as a causative factor in suicide was high among the elderly, but among the other age groups this factor trailed behind economic difficulties for men and psychiatric disorders for women. To prevent suicide, social cooperation as well as a plenitude of visiting nurses and psychiatric care is required, and early detection and treatment are also important.

Adult↗

Curcumin treatment abrogates endoplasmic reticulum retention and aggregation-induced apoptosis associated with neuropathy-causing myelin protein zero-truncating mutants.

Mutations in MPZ, the gene encoding myelin protein zero (MPZ), the major protein constituent of peripheral myelin, can cause the adult-onset, inherited neuropathy Charcot-Marie-Tooth disease, as well as the more severe, childhood-onset Dejerine-Sottas neuropathy and congenital hypomyelinating neuropathy. Most MPZ-truncating mutations associated with severe forms of peripheral neuropathy result in premature termination codons within the terminal or penultimate exons that are not subject to nonsense-mediated decay and are stably translated into mutant proteins with potential dominant-negative activity. However, some truncating mutations at the 3' end of MPZ escape the nonsense-mediated decay pathway and cause a mild peripheral neuropathy phenotype. We examined the functional properties of MPZ-truncating proteins that escaped nonsense-mediated decay, and we found that frameshift mutations associated with severe disease cause an intracellular accumulation of mutant proteins, primarily within the endoplasmic reticulum (ER), which induces apoptosis. Curcumin, a chemical compound derived from the curry spice tumeric, releases the ER-retained MPZ mutants into the cytoplasm accompanied by a lower number of apoptotic cells. Our findings suggest that curcumin treatment is sufficient to relieve the toxic effect of mutant aggregation-induced apoptosis and may potentially have a therapeutic role in treating selected forms of inherited peripheral neuropathies.

Apoptosis↗

Visualization of temporal increase in compound nerve action magnetic fields in the human median nerve during ischemia.

We studied the variation in the human median nerve activity during ischemia by measuring compound nerve action magnetic fields (CAFs). Temporal increases in the CAF during ischemia were successfully visualized on isofield contour maps. Intense paresthesias were induced after 29 +/- 5 s (mean +/- SD) of ischemia, which consistently reached a maximum after 4 min 55 +/- 12 s. The variations in CAFs were consistent with changes in sensory perception. The hyperexcitability in large myelinated axons can be visualized as temporary increases in CAF. These results are the first to demonstrate the efficacy of magnetic-recording techniques, which allow monitoring of changes in neural activity.

Adult↗

Activation of human SII cortex during exploratory finger movement and hand clenching tasks.

We used electric median nerve stimuli to elucidate the functional properties of neurons in the human secondary somatosensory cortex during exploration of small objects and muscle contraction. Somatosensory evoked fields were recorded from nine healthy subjects with a 204-channel neuromagnetometer. Electrical stimuli were applied once every 3 s to the left median nerve at the wrist. The conditions during the stimulation were rest (control session), exploration of small objects (exploration session) and clenching the hand while the wrist was being electrically stimulated (clench session). The strengths of equivalent current dipoles of evoked fields from the secondary somatosensory cortex were increased during the exploration session, but those of evoked fields were decreased by the clench session.

Adult↗

Difference in somatosensory evoked fields elicited by mechanical and electrical stimulations: Elucidation of the human homunculus by a noninvasive method.

We recently recorded somatosensory evoked fields (SEFs) elicited by compressing the glabrous skin of the finger and decompressing it by using a photosensor trigger. In that study, the equivalent current dipoles (ECDs) for these evoked fields appeared to be physiologically similar to the ECDs of P30m in median nerve stimulation. We sought to determine the relations of evoked fields elicited by mechanically stimulating the glabrous skin of the great toe and those of electrically produced P40m. We studied SEFs elicited by mechanical and electrical stimulations from the median and tibial nerves. The orientations of dipoles from the mechanical stimulations were from anterior-to-posterior, similar to the orientations of dipoles for P30m. The direction of the dipole around the peak of N20m from median nerve electrical stimulation was opposite to these directions. The orientations of dipoles around the peak of P40m by tibial nerve stimulation were transverse, whereas those by the compression and decompression stimulation of the toe were directed from anterior-to-posterior. The concordance of the orientations in ECDs for evoked fields elicited by mechanical and electrical stimulations suggests that the ECDs of P40m are physiologically similar to those of P30m but not to those of N20m. The discrepancy in orientations in ECDs for evoked field elicited by these stimulations in the lower extremity suggests that electrical and compression stimulations elicit evoked fields responding to fast surface rubbing stimuli and/or stimuli to the muscle and joint.

Adult↗