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Biomedical subjects

S Ohara

Publications and source records attributed to S Ohara.

At least 19 recordsLinked to original sources

Internal pallidal neuronal activity during mild drug-related dyskinesias in Parkinson's disease: decreased firing rates and altered firing patterns.

The neuronal basis of hyperkinetic movement disorders has long been unclear. We now test the hypothesis that changes in the firing pattern of neurons in the globus pallidus internus (GPi) are related to dyskinesias induced by low doses of apomorphine in patients with advanced Parkinson's disease (PD). During pallidotomy for advanced PD, the activity of single neurons was studied both before and after administration of apomorphine at doses just adequate to induce dyskinesias (21 neurons, 17 patients). After the apomorphine injection, these spike trains demonstrated an initial fall in firing from baseline. In nine neurons, the onset of on was simultaneous with that of dyskinesias. In these spike trains, the initial fall in firing rate preceded and was larger than the fall at the onset of on with dyskinesias. Among the three neurons in which the onset of on occurred before that of dyskinesias, the firing rate did not change at the time of onset of dyskinesias. After injection of apomorphine, dyskinesias during on with dyskinesias often fluctuated between transient periods with dyskinesias and those without. Average firing rates were not different between these two types of transient periods. Transient periods with dyskinesias were characterized by interspike interval (ISI) independence, stationary spike trains, and higher variability of ISIs. A small but significant group of neurons demonstrated recurring ISI patterns during transient periods of on with dyskinesias. These results suggest that mild dyskinesias resulting from low doses of apomorphine are related to both low GPi neuronal firing rates and altered firing patterns.

Aged↗

Analysis of synchrony demonstrates 'pain networks' defined by rapidly switching, task-specific, functional connectivity between pain-related cortical structures.

Imaging studies indicate that experimental pain is processed in multiple cortical areas which are often characterized as a network. However, the functional connectivity within the network and the other properties of the network is poorly understood. Substantial evidence demonstrates that synchronous oscillations between two cortical areas may indicate functional connectivity between those areas. We test the hypothesis that cortical areas with pain-related activity are functionally connected during attention to a painful stimulus. We stimulated with a painful, cutaneous, laser stimulus and recorded the response directly from the cortical surface (electrocorticography--ECoG) over primary somatosensory (SI), parasylvian (PS), and medial frontal (MF) cortex through subdural electrodes implanted for treatment of epilepsy. The results demonstrate synchrony of ECoGs between cortical structures receiving input from nociceptors, as indicated by the occurrence of laser-evoked potentials (LEPs) and/or event-related desynchronization (ERD). Prior to the stimulus, directed attention to the painful stimulus consistently increased the degree of synchrony between SI and PS regions, as the subject anticipated the stimulus. After the laser stimulus, directed attention to the painful stimulus consistently increased the degree of synchrony between SI and MF cortex, as the subject responded by counting the stimulus. Therefore, attention to painful stimuli always enhanced synchrony between cortical pain-related structures. The pattern of this synchrony changed as the patient switched tasks from anticipation of the stimulus to counting the stimulus. These results are the first compelling evidence of pain networks characterized by rapidly switching, task-specific functional connectivity.

Adult↗

Aseptic meningo-radiculo-encephalitis presenting initially with urinary retention: a variant of acute disseminated encephalomyelitis.

We report three male patients with aseptic meningoencephalo- radiculitis presenting with acute urinary retention. Viral antibody titers for herpes types I and II and the PCR studies were negative. The cerebrospinal fluid revealed elevated myelin basic protein. The serum antibodies against a panel of gangliosides, some of which are known to be associated with acquired demyelinating neuropathies, were all negative. The magnetic resonance imaging (MRI) studies revealed spotty T2 high intensities in the basal ganglia, thalamus and brainstem in two patients. In one patient,meningeal gadolinium enhancement of the conus and cauda equina of the spinal cord was recognized. On urodynamic studies, all patients showed features of atonic bladder with or without detrusor hyperactivity. They were treated conservatively without using steroids or immunoglobulins, and made a remarkable functional recovery with the disappearance of abnormal MRI findings.However, all three were left with erectile dysfunction, and two continued to use self-intermittent catheterization at more than 3-year follow-up. There was no recurrence of symptoms. The underlying causes remain unclear, though they may represent a variant of acute disseminated encephalomyelitis.

Adult↗

Modulation of somatosensory event-related potential components in a tactile-visual cross-modal task.

Human tactile discrimination studies have shown that visual stimuli enhance tactile performance. Other studies on event-related potentials showed that somatosensory N140 was enhanced when attention of human subjects was directed to tactile stimuli. Therefore, we hypothesized that N140 would be modulated when human subjects performed tactile cross-modal delay tasks. Scalp-event-related potentials were recorded from normal subjects performing either a tactile-tactile unimodal, or a tactile-visual cross-modal delayed matching-to-sample task. Identical tactile stimuli were used in both tasks. N140 component evoked by the tactile stimuli was enhanced in the cross-modal task. Enhancement of this component was also observed in control cross-modal tasks. The results suggest that tactile-visual cross-modal association affects tactile sensory-perceptual processes in humans.

Adult↗

Psychophysics of CNS pain-related activity: binary and analog channels and memory encoding.

The forebrain neuronal system signaling pain has been poorly characterized. The pain pathway afferent to the thalamus may be a labeled line consisting of neurons in the pain-signaling pathway to the brain (spinothalamic tract, STT) that respond only to painful stimuli. It has recently been proposed that the STT contains a series of analog-labeled lines, each signaling a different aspect of the internal state of the body (interoception), for example, visceral/cold/itch sensations. In this view, pain is the unpleasant emotion produced by disequilibrium of the internal state. The authors now show that stimulation of an STT receiving zone (thalamic principal somatic sensory nucleus, ventral caudal) in awake humans produces two different exteroceptive responses. The first is a binary response signaling the presence of painful stimuli. The second is an analog response in which nonpainful and painful sensations are graded with intensity of the stimulus. Such stimulation can evoke both the sensory and emotional components of previously experienced pain. These results illustrate the diverse functions of human pain signaling pathways.

Animals↗

Sequential neural processes of tactile-visual crossmodal working memory.

Working memory is essential to learning and performing sensory-motor behaviors that in many situations require the integration of stimuli of one modality with stimuli of another. In the present study, we focused on the neural mechanisms underlying crossmodal working memory. We hypothesized that in performance of the tactile crossmodal working memory task, there would be sequentially discrete task-correlated neural activities representing the processes of crossmodal working memory. Scalp-recorded event-related potentials were collected from 15 electrodes in humans performing each of four tasks: tactile-tactile unimodal delayed matching-to-sample task, tactile-visual crossmodal delayed matching-to-sample task, tactile unimodal control spatial task, and tactile crossmodal control spatial task. Two positive event-related potential peaks were observed during the delay of the task. One peak (late positive component-1) was at about 330 ms after the onset of the tactile stimulus, and the other (late positive component-2) was at about 600 ms. Late positive component-1 was observed in all four tasks. There was no significant difference in late positive component-1 either between the unimodal tasks, or between the crossmodal tasks, but late positive component-1 was significantly larger in the crossmodal tasks than that in the unimodal tasks, and showed a specific pattern of larger activity over parietal areas than activity over frontal areas. Late positive component-2 was not observed in the unimodal matching task but was observed in all other three tasks over parietal areas. During the late delay (1000 ms-1500 ms), significant differences in negative potentials (late negative component) were found between the tasks. The present study shows sequential changes in event-related potentials during the retention period of working memory tasks. It indicates that in performance of a crossmodal working memory task, there are sequentially discrete neural processes that may represent neural activities related to different cognitive functions, such as crossmodal transfer of information, and the working memory of the stimulus.

Adult↗

Psychophysical elements of place and modality specificity in the thalamic somatic sensory nucleus (ventral caudal, vc) of awake humans.

Discrete anatomic structures in the monkey somatic sensory thalamus may segregate input arising from different peripheral receptors and from different parts of the body. It has been proposed that these structures serve as components of modality- and place-specific pathways from the periphery to the cortex. We now test this hypothesis by examining the modality- and place-specific segregation of sensations at sites where microstimulation (microA currents) within the region of ventral caudal (Vc; human principal somatic sensory nucleus) evokes somatic sensations. Microstimulation was delivered in an ascending staircase protocol consisting of different numbers of pulses (4-100) presented at different frequencies (10-200 Hz) during awake thalamic surgery for movement disorders. The results demonstrate that the part of the body where microstimulation evoked sensation (projected field) and the descriptors of nonpainful sensations were usually uniform across the staircase. These results strongly support the existence of psychophysical elements of place and modality specificity in the Vc thalamus. The proportion of sites at which the sensation included more than one part of the body almost always stayed constant over current intervals (plateaus) of 10 microA. Similar plateaus were not found for sites with more than one descriptor, suggesting that elements of modality-specificity are smaller than and located within those for place-specificity. The intensity of sensations varied with the number of stimulation pulses for mechanical/tingle and cool sensations. The results provide strong evidence for psychophysically defined elements that are responsible for modality specificity of nonpainful sensations, place specificity, and intensity coding of somatic sensation in the human thalamus.

Deep Brain Stimulation↗

Pain and temperature encoding in the human thalamic somatic sensory nucleus (Ventral caudal): inhibition-related bursting evoked by somatic stimuli.

Stimulus-evoked inhibitory events have not been demonstrated in thalamic spike trains encoding of pain and temperature stimuli. We have now tested the hypothesis that the human thalamic response to mechanical and thermal stimuli is characterized by low-threshold calcium spike (LTS)-associated bursts of high-frequency action potentials preceded by prolonged inhibition. The results included 57 neurons recorded in the human thalamic principal somatic sensory nucleus (ventral caudal, Vc) of 24 patients during awake surgery. Neurons were classified by the grading of their response with stimulus intensity into the painful range (graded or non-graded) and the stimulus response (to mechanical, cold, or heat stimuli). Firing rates were analyzed by the response to all stimuli combined (stimuli overall) and to the stimulus characteristic of the stimulus response type (optimal stimulus), e.g., cold stimuli for neurons of the cold stimulus response type. All neuronal categories had clear stimulus-evoked LTS bursting as identified by the criteria for selecting bursts in the spike train, by significant preburst inhibition, and by preburst inter-spike interval not significantly <100 ms. Stimulus-evoked LTS burst rates were significantly higher for neurons in the cold stimulus response type independent of the firing rate between bursts. The parameters of preburst inhibition were largely independent of the neuronal category and the stimuli included in the analysis, which suggests inhibitory mechanisms are similar across neuronal types. Therefore LTS bursting is a substantial, nonlinear component of the spontaneous and stimulus-evoked activity of thalamic neurons in awake humans.

Action Potentials↗

Diffusion of cytotoxic concentrations of nitric oxide generated luminally at the gastro-oesophageal junction of rats.

BACKGROUND: In humans, high concentrations of nitric oxide are generated luminally at the gastro-oesophageal junction through enterosalivary recirculation of dietary nitrate. AIM: To investigate whether luminal nitric oxide can diffuse into the adjacent digestive tissue and alter tissue integrity. METHODS: We designed an animal model using Wistar rats in which physiological concentrations of nitrite and acidified ascorbic acid were administered separately so that the two reactants first meet to form nitric oxide at the gastro-oesophageal junction. Luminal and tissue concentrations of nitric oxide were measured with an electrode and an electron paramagnetic resonance spectrometer, respectively. Concentrations of glutathione in the tissue were measured as a marker of nitrosative stress. RESULTS: High concentrations of luminal nitric oxide were generated locally at the gastro-oesophageal junction of nitrite administered rats, reproducing a phenomenon observed in humans. High levels of nitric oxide were also detected largely in the superficial epithelium of the gastro-oesophageal junction. The concentration of tissue glutathione at the gastro-oesophageal junction was significantly lower in nitrite administered rats compared with control rats, whereas that in the distal stomach was similar in the two rat groups. CONCLUSIONS: Using an animal model, this study demonstrated that nitric oxide generated in the lumen diffuses into the adjacent gastric tissue to a substantial degree, leading to localised consumption of glutathione in the tissue. Nitrosative stress induced by this mechanism may be involved in the high prevalence of inflammation and metaplasia, and subsequent development of neoplastic disease at this site.

Animals↗

The polymorphism interleukin 8 -251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population.

BACKGROUND: Helicobacter pylori infection is associated with variable clinical outcomes, including gastroduodenal diseases, and genetic factors may be relevant in this process. AIMS: We investigated the effects of an interleukin 8 (IL-8) gene polymorphism on the risk of gastroduodenal diseases, the degree of H pylori induced gastritis, and IL-8 gene transcription. SUBJECTS: The study was performed in 244 healthy control subjects and 690 H pylori positive patients with non-cardia gastric cancer, gastric ulcer, duodenal ulcer, or gastritis. METHODS: We identified the IL-8 -251 A/T polymorphism by direct sequence analysis, and measured the gastritis score and serum pepsinogen (PG). The transcriptional promoter activity of the IL-8 gene was assessed by luciferase assay. RESULTS: IL-8 -251A was associated with a higher risk of gastric cancer and gastric ulcer. Patients carrying IL-8 -251A showed an increased risk of gastric cancer (odds ratios (OR) 2.01 (95% confidence interval (CI) 1.38-2.92)) and gastric ulcer (OR 2.07 (95% CI 1.37-3.12)). Compared with patients younger than 49 years, atrophy and metaplasia scores in the antrum were significantly higher and the PG I/II ratio significantly lower in -251A carriers than in T/T carriers. In the in vitro assay, IL-8 -251A showed enhanced promoter activity in response to IL-1beta or tumour necrosis factor alpha. CONCLUSIONS: The IL-8 -251A allele may be associated with progression of gastric atrophy in patients with H pylori infection, and may increase the risk of gastric cancer and gastric ulcer in Japanese people.

Adolescent↗

Long-term effect of Helicobacter pylori eradication on the reversibility of acid secretion in profound hypochlorhydria.

BACKGROUND: Although profound hypochlorhydria is considered to be an important risk factor for development of gastric cancer, long-term effect of Helicobacter pylori eradication on its reversibility remains uncertain. AIM: To clarify the change in acid secretion after eradication in a long-term follow-up over 5 years in patients with profound hypochlorhydria. METHODS: Twenty-three H. pylori-positive patients with hypochlorhydria (<0.6 mmol/10 min) were enrolled prospectively. Assessment of gastrin-stimulated acid output and histologic evaluation of biopsy specimens were performed prior to, and 1, 7 months after eradication. Subsequently, gastric acid secretion was assessed for long-term period over 5 years after eradication in 12 patients. RESULTS: Gastric acid secretion was reversed to normal range in nine of 23 patients (39%) at 7 months after eradication. In the long-term follow-up, gradual and significant recovery in gastric acid secretion was observed up to 2 years post-therapy. However, there was no additional increase during the last 3 years of 5-year follow-up period, leaving the acid secretory levels subnormal in the majority of the patients. CONCLUSIONS: This long-term follow-up study suggests that the pathologic process has already progressed to an irreversible stage in the majority of H. pylori-positive patients with marked body atrophy and profound hypochlorhydria.

Achlorhydria↗

Attention to a painful cutaneous laser stimulus modulates electrocorticographic event-related desynchronization in humans.

OBJECTIVE: To test the hypothesis that attention to painful cutaneous laser stimuli enhances event-related desynchronization (ERD) in cortical regions receiving nociceptive input. METHODS: We used wavelet time-frequency analysis and bandpass filtering to measure ERD quantitatively in subdural electrocorticographic recordings while subjects either attended to, or were distracted from, a painful cutaneous laser stimulus. RESULTS: ERD were observed over primary somatosensory and parasylvian (PS) cortices in all 4 subjects, and over medial frontal cortex in 1 subject. Laser-evoked potentials were also observed in all 3 regions. In all subjects, ERD was more widespread and intense, particularly over PS, during attention to laser stimuli (counting stimuli) than during distraction from the stimuli (reading for comprehension). CONCLUSIONS: These findings suggest that pain-associated ERD is modulated by attention, particularly over PS. SIGNIFICANCE: This study suggests that thalamocortical circuits are involved in attentional modulation of pain because of the proposed role of these circuits in the mechanisms of ERD.

Adult↗

Subregions of human MT complex revealed by comparative MEG and direct electrocorticographic recordings.

OBJECTIVE: To locate the visual motion complex (MT+) and study its response properties in an epilepsy surgery patient. METHODS: A 17-year-old epilepsy patient underwent invasive monitoring with subdural electrodes in the right temporo-parieto-occipital area. MT+ was investigated by cortical electric stimulation and by epicortical visual evoked potentials time-locked to motion onset of sinusoidal gratings (motion VEP). Motion-related visual evoked magnetic field (motion VEF) was also recorded before the electrode implantation to complement the invasive recording. RESULTS: Motion VEPs revealed two subregions within MT+, generating early and late potentials respectively. The early activity with a peak around 130 ms was localized at a single electrode situated immediately caudal to the initial portion of the ascending limb of the superior temporal sulcus (AL-STS). The late activity, peaking at 242-274 ms, was located ventro-rostrally over three electrodes. Among the four electrodes with motion VEPs, cortical stimulation at the most caudal pair elicited motion-in-depth perception involving the whole visual field. In addition to two subregions revealed on the gyral crown, magnetoencephalography (MEG) demonstrated another subregion with a late motion VEF in AL-STS immediately rostral to the electrode with the early motion VEP. CONCLUSIONS: In combination with MEG recording, the present invasive exploration demonstrated human MT+ in a focal area of the temporo-parieto-occipital junction and delineated possible three subregions as indicated by the different latencies and distributions of the motion VEP/VEFs. SIGNIFICANCE: Comparative MEG and direct electrocorticographic recordings delineated possible subregions within the human MT complex.

Adolescent↗

Short-term effect of buformin, a biguanide, on insulin sensitivity, soluble fraction of tumor necrosis factor receptor and serum lipids in overweight patients with type 2 diabetes mellitus.

AIMS/HYPOTHESIS: The UK Prospective Diabetes Study (UKPDS) showed that biguanide therapy in overweight patients reduced the risk for any diabetes-related endpoint and all-cause mortality. Biguanides lower the blood glucose values without stimulation of insulin release. We have investigated the short-term effect of buformin on insulin sensitivity, solved tumor necrosis factor receptors (sTNFRs), and serum lipids in overweight subjects with type 2 diabetes mellitus (DM). METHOD: Thirteen overweight subjects with type 2 DM were examined. The subjects who were fed 20 kcal/kg body weight were divided into two subgroups according to whether they were treated by buformin (Buformin group), or dietary therapy alone (Diet group). Six patients were in Buformin group and seven patients were in Diet group. We calculated insulin-mediated glucose uptake by the liver and peripheral tissues using euglycemic hyperinsulinemic clamp combined with an oral glucose load before and after buformin treatment or diet therapy for 2 weeks. RESULTS: Fasting plasma glucose, total cholesterol (T-chol), LDL-cholesterol (LDL-chol), and sTNFR2 were significantly decreased, and hepatic glucose uptake significantly increased from 32 +/- 7 to 42 +/- 7% (P < 0.05) in Buformin group but did not changed significantly in Diet group. However, the glucose infusion rate thought to express insulin sensitivity in peripheral tissue, TNF-alpha, sTNFR1, fasting plasma insulin, C-peptide, and NEFA levels did not change significantly in both the groups after treatment. CONCLUSION/INTERPRETATION: Buformin improved insulin sensitivity in the liver and decreased T-chol, LDL-chol, and sTNFR2. The mechanism of action for buformin likely involves inhibition of TNF-alpha. Buformin lowers insulin resistance and risk factors for cardiovascular disease including serum lipid and will therefore, be useful in management of overweight type 2 DM patients.

Buformin↗

Allodynia in patients with post-stroke central pain (CPSP) studied by statistical quantitative sensory testing within individuals.

The disinhibition hypothesis of post-stroke central pain (CPSP) suggests that 'the excessive response (dysesthesia/hyperalgesia/allodynia) is accompanied by a em leader loss of sensation' resulting from a lesion of a 'lateral nucleus' of thalamus or of 'cortico-thalamic paths' [Brain 34 (1911) 102]. One recent elaboration of this hypothesis proposes a submodality specific relationship, such that injury to a cool-signaling lateral thalamic pathway disinhibits a nociceptive medial thalamic pathway, thereby producing both burning, cold, ongoing pain and cold allodynia. The current study quantitatively evaluated the sensory loss and sensory abnormalities to discern submodality relationships between these sensory features of CPSP. The present results were statistically tested within individuals so that sensory loss and sensory abnormality are directly related by occurrence in the same individual. The results demonstrate that individuals with CPSP and normal tactile detection thresholds experience tactile allodynia significantly more often than those with tactile hypoesthesia. Most patients (11/13) exhibited hypoesthesia for the perception of cool stimuli, but few of these (2/11) showed cold allodynia. The most dramatic case of cold allodynia occurred in a patient who had a normal detection threshold for cold. Individuals with cold hypoesthesia, strictly contralateral to the cerebro-vascular accident (CVA or stroke), were often characterized by the presence of burning, cold, ongoing pain, and by the absence, not the presence, of cold allodynia. Overall, these results in CPSP suggest that tactile allodynia occurs in disturbances of thermal/pain pathways that spare the tactile-signaling pathways, and that cold hypoesthesia is neither necessary nor sufficient for cold allodynia.

Adult↗

Amplitudes of laser evoked potential recorded from primary somatosensory, parasylvian and medial frontal cortex are graded with stimulus intensity.

Intensity encoding of painful stimuli in many brain regions has been suggested by imaging studies which cannot measure electrical activity of the brain directly. We have now examined the effect of laser stimulus intensity (three energy levels) on laser evoked potentials (LEPs) recorded directly from the human primary somatosensory (SI), parasylvian, and medial frontal cortical surfaces through subdural electrodes implanted for surgical treatment of medically intractable epilepsy. LEP N2* (early exogenous/stimulus-related potential) and LEP P2** (later endogenous potential) amplitudes were significantly related to the laser energy levels in all regions, although differences between regions were not significant. Both LEP peaks were also significantly correlated with the pain intensity evoked by the laser stimulus, excepting N2* over the parasylvian region. Peak latencies of both LEP peaks were independent of laser energy levels. N2* and P2** amplitudes of the maxima in all regions showed significant positive linear correlations with laser energy, excepting N2* over the parasylvian region. The lack of correlation of parasylvian cortical N2* with laser energy and pain intensity may be due to the unique anatomy of this region, or the small sample, rather than the lack of activation by the laser. Differences in thresholds of the energy correlation with amplitudes were not significant between regions. These results suggest that both exogenous in endogenous potentials evoked by painful stimuli, and recorded over SI, parasylvian, and medial frontal cortex of awake humans, encode the intensity of painful stimuli and correlate with the pain evoked by painful stimuli.

Adult↗

Gastric acid secretion of normal Japanese subjects in relation to Helicobacter pylori infection, aging, and gender.

BACKGROUND: In Japan, where the incidence of gastric cancer is high, Helicobacter pylori infection could affect gastric acid secretion differently from that in Western countries. The aim of this study was to investigate the relationship between H. pylori infection, acid secretion, aging, and gender in normal Japanese subjects. METHODS: The study comprised 193 Japanese subjects who had undergone routine endoscopy. Gastrin-stimulated acid output was performed during the routine endoscopic examination using the endoscopic method of gastric acid secretory testing (EGT: endoscopic gastrin test), which has been reported previously. H. pylori status was determined by histology, rapid urease test, and serology. RESULTS: Mean EGT values were 3.9 +/- 1.5 mEq/10 min in H. pylori-negative men, 1.6 +/- 2.5 in H. pylori-positive men, 2.2 +/- 0.9 in H. pylori-negative women, and 1.5 +/- 1.2 in H. pylori-positive women. Although acid secretion was lower in H. pylori-positive subjects compared with H. pylori-negative subjects in both men and women, the decrease was more marked in men with H. pylori infection. Multiple linear regression analysis showed that aging is positively associated with gastric acid secretion in the H. pylori-negative subjects, whereas a negative association was found between them in the H. pylori-positive subjects. CONCLUSIONS: In Japanese subjects, aging affects gastric acid secretion differently depending on the status of H. pylori infection. H. pylori infection showed a stronger inhibitory effect on the acid secretion in men than in women. This gender-related difference in the susceptibility of acid secretion to H. pylori infection may explain the higher rates of gastric cancer in men in Japan.

Adult↗