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Biomedical subjects

Akemi Tomoda

Publications and source records attributed to Akemi Tomoda.

10 recordsLinked to original sources

Neurobiological consequences of early stress and childhood maltreatment: are results from human and animal studies comparable?

Recent studies have reported an association between exposure to childhood abuse or neglect and alterations in brain structure or function. One limitation of these studies is that they are correlational and do not provide evidence of a cause-effect relationship. Preclinical studies on the effects of exposure to early life stress can demonstrate causality, and can enrich our understanding of the clinical research if we hypothesize that the consequences of early abuse are predominantly mediated through the induction of stress responses. Exposure to early abuse and early stress has each been associated with the emergence of epileptiform electroencephalogram (EEG) abnormalities, alterations in corpus callosum area, and reduced volume or synaptic density of the hippocampus. Further, there is evidence that different brain regions have unique periods when they are maximally sensitive to the effects of early stress. To date, preclinical studies have guided clinical investigations and will continue to provide important insight into studies on molecular mechanisms and gene-environment interactions.

Animals↗

Daily expression of clock genes in whole blood cells in healthy subjects and a patient with circadian rhythm sleep disorder.

In recent years, circadian rhythm sleep disorders in humans have been increasing. Clinical features characteristic of this disorder are well known, but the specific causes remain unknown. However, various derangements of circadian expression of the clock gene are a probable cause of this disease. We have attempted to elucidate the relationship between the expression of the clock genes in whole blood cells and the clinical features characteristic of this disorder. In this study, we indicate the daily expression of clock genes period (Per) 1, 2, 3, Bmal1, and Clock in whole blood cells in 12 healthy male subjects. The peak phase of Per1, Per2, and Per3 appeared in the early morning, whereas that of Bmal1 and Clock appeared in the midnight hours. Furthermore, in one patient case with circadian rhythm sleep disorder, we observed variations of the peak phase in clock genes by treatments such as light therapy, exercise therapy, and medicinal therapy. This study suggested that the monitoring of human clock genes in whole blood cells, which may be functionally important for the molecular control of the circadian pacemaker as well as in suprachiasmatic nucleus, might be useful to evaluate internal synchronization.

ARNTL Transcription Factors↗

Cytokine production and modulation: comparison of patients with chronic fatigue syndrome and normal controls.

We studied cytokine production in 15 patients with chronic fatigue syndrome (CFS) and 23 controls. CFS patients' peripheral blood mononuclear cells were cultured with lipopolysaccharide or phytohemagglutinin. Enzymatic immunoassay indicated cytokine concentration in culture supernatants. CFS patients showed significantly lower mRNA levels and transforming growth factor-beta1 (TGF-beta1) production. Cytokine dysregulation affects CFS pathogenesis. TGF-beta1 may aid treatment because it affects CFS inflammatory characteristics.

Adult↗

Learning and memorization impairment in childhood chronic fatigue syndrome manifesting as school phobia in Japan.

For the last 15 years, we have tried to understand the pathophysiology of childhood chronic fatigue syndrome (CCFS) in Japan. In this condition, two major symptoms are important: easy fatigability and disturbed learning and memorization. In CCFS patients we clinically evaluated autonomic nervous system function, circadian rhythm of hormonal secretion (melatonin, cortisol and 3-endorphin), core body temperature, and sleep-wake pattern. Most patients showed autonomic nervous system dysfunction and circadian rhythm disturbances, similar to those observed in jet lag. Radiological imaging studies (SPECT, Xe-CT, and MRS) revealed decreased blood flow in the frontal and thalamic areas, and accumulation of choline in the frontal lobe. We analyzed the relationship between the laboratory data and clinical symptoms in CCFS.

Adolescent↗

Pharmacokinetics and effects of ribavirin following intraventricular administration for treatment of subacute sclerosing panencephalitis.

Ribavirin is a broad-spectrum antiviral drug with inhibitory activity against many RNA viruses, including measles virus. Five patients with subacute sclerosing panencephalitis (SSPE) were treated with ribavirin by intraventricular administration. Although there were transient side effects attributed to ribavirin, such as drowsiness, headache, lip and gingival swelling, and conjunctival hyperemia, intraventricular ribavirin therapy was generally safe and well tolerated. The cerebrospinal fluid (CSF) ribavirin concentration decreased, as described by a monoexponential function, after a single intraventricular dose. There was considerable interindividual variability, however, in the peak level and half-life. We aimed to adjust the individual dose and frequency of intraventricular administration based on the peak level and half-life of ribavirin in the CSF in order to maintain the CSF ribavirin concentration at the target level. Clinical effectiveness (significant neurologic improvement and/or a significant decrease in titers of hemagglutination inhibition antibodies against measles virus in CSF) was observed for four of five patients. For these four patients, CSF ribavirin concentrations were maintained at a level at which SSPE virus replication was almost completely inhibited in vitro and in vivo, whereas the concentration was lower in the patient without clinical improvement. These results suggest that intraventricular administration of ribavirin is effective against SSPE if the CSF ribavirin concentration is maintained at a high level. Intraventricular ribavirin therapy should be pursued further for its potential use for patients with SSPE and might be applied in the treatment of patients with encephalitis caused by other RNA viruses.

Adolescent↗

Combination therapy with intraventricular interferon-alpha and ribavirin for subacute sclerosing panencephalitis and monitoring measles virus RNA by quantitative PCR assay.

Subacute sclerosing panencephalitis (SSPE) is a degenerative disease of the central nervous system that leads to death within a few years. Recently, it has been reported that combination therapy with intraparenchymal interferon-alpha (INF-alpha) and intraventricular ribavirin is effective. An 11-year-old SSPE patient whose clinical symptoms progressed rapidly, was treated first with intraventricular INF-alpha and then with combined intraventricular INF-alpha and ribavirin therapy. To monitor viral load over the course of the therapy, measles virus RNA was quantified using a real-time polymerase chain reaction assay. Measles virus RNA decreased rapidly after the INF-alpha therapy was started, paralleling the decrease in the measles antibody titer in the cerebrospinal fluid and the improvement in the neurological disability. After intraventricular ribavirin was combined with INF-alpha therapy, no further improvement was observed. The neurological disability gradually progressed, although the amount of virus RNA remained low.

Antiviral Agents↗

Case study: differences in human Per2 gene expression, body temperature, cortisol, and melatonin parameters in remission and hypersomnia in a patient with recurrent hypersomnia.

Recurrent hypersomnia is characterized by recurring episodes of hypersomnia of 18 h or more per day lasting from several days to several weeks. We report the case of a 17-year-old male subject with recurrent hypersomnia who displayed change in the 24 h expression of the hPer2 gene in whole red and white blood cells as well as markers [deep body temperature (DBT) and cortisol] of the circadian time structure during an episode of hypersomnia compared to remission. The patient was studied for the temporal characteristics of hPer2 gene, DBT, cortisol, and melatonin expression during a single 24 h span during an episode of hypersomnia and again during a single 24 h span in the following remission. The approximation of a 24 h cosine curve to the time series data revealed circadian rhythmicity (P < 0.05) only in DBT in the two stages of the disease with differences in amplitude and acrophase. Cortisol circadian rhythmicity was detected during remission, but not during hypersomnia. Statistically significant differences were detected by ANOVA between the remission and active disease stages in the 24 h mean level of hPer2 gene expression (P < 0.05), cortisol (P < 0.05), and DBT (P < 0.05). The findings of this case study suggest the expression of hPer2 gene and alterations in circadian time structure might play an important role in the pathogenesis of recurrent hypersomnia, although additional study is required.

Adolescent↗

[Trial of intraventricular ribavirin and interferon-alpha combination therapy for subacute sclerosing panencephalitis (SSPE) in Japan].

A survey was made on 10 patients with subacute sclerosing panencephalitis (SSPE) during the last four years from the viewpoint of clinical safety of ribavirin therapy in Japan. Although the age of onset, latent period, and effectiveness were variable among the cases, they were treated safely with intraventricular ribavirin combined with high doses of interferon (IFN). Their clinical stages on admission ranged from the first to fourth of Jabbour's classification, and those on the beginning of ribavirin therapy also ranged from the first to fourth. Seven of them were first treated with intraventricular IFN-alpha monotherapy, however, the combination of intraventricular IFN-alpha and ribavirin was started after clinical worsening. Although 5 patients showed slow progression, seven responded to the therapy with clinical improvement or decreased measles antibody titers in the CSF. Especially, one patient showed improvement to Jabbour's first stage and no further progression during the following 3 years. Ribavirin therapy caused no severe effects. Lip swelling (50%), sleepiness (40%), and headache (30%) were noted. Although we were unable to perform a double-blinded clinical study for ethical reasons, our results suggest that treatment with intraventricular ribavirin and high doses of IFN may be effective for SSPE. Early administration of intraventricular ribavirin and IFN might be considered especially to IFN in non-responders. To establish this combination therapy as a safe and effective treatment of SSPE, further studies are necessary on the role of ribavirin in the pathogenesis as well as its effects in the central nervous system.

Adolescent↗

[Spinal cord stimulation for complex regional pain syndrome: report of 2 cases].

Two adolescents with complex regional pain syndrome (CRPS) were treated safely and effectively by spinal cord stimulation (SCS). They complained of intractable pain resistant to conservative therapies. Whereas continuous epidural anesthesia temporarily reduced pain, SCS was more effective in alleviating chronic severe pain and improving the quality of life. With careful selection of patients, SCS therapy might be recommended even in young cases.

Adolescent↗