Evaluation of patient dose for barium enemas and CT colonography in Japan.

The objective of this study was to assess patient doses for examinations of the lower digestive tract (barium enemas and CT colonography) in Japan. These doses were evaluated from in-phantom dose measurements using a dosemeter-implanted anthropomorphic phantom and from the knowledge of procedures of these examinations. For barium enemas, the doses, which were the sums of doses for various projections in the procedure, were separately derived for fluoroscopy and for analogue and digital radiography. For CT colonography, the doses were evaluated for the prone and the supine positions, each including the doses by scout imaging, and a single abdominal scan for routine and low-dose set-ups. For barium enemas, maximum local skin doses were less than 100 mGy despite relatively long average fluoroscopy times of 8 min; organ doses ranged from 9-26 mGy in the abdomen. The effective dose of 10.7 mSv for analogue radiography decreased by 12% when digital radiography was used, although more than 80% of the dose was due to fluoroscopy. In routine CT colonography performed using a relatively high mean effective mAs of 119 for the accurate detection of colorectal cancer and extra colonic lesions, organ doses within the primary X-ray beam were between 30 mGy and 44 mGy for paired scans whereas, in a low-dose set-up with an effective mAs of 27, they were approximately 10 mGy. Effective doses for routine and low-dose CT colonography of 23.4 mSv and 5.7 mSv were about double and half of the doses for barium enemas, respectively.

Neural correlates of auditory feedback control in human.

Auditory feedback plays an important role in natural speech production. We conducted a functional magnetic resonance imaging (fMRI) experiment using a transformed auditory feedback (TAF) method to delineate the neural mechanism for auditory feedback control of pitch. Twelve right-handed subjects were required to vocalize /a/ for 5 s, while hearing their own voice through headphones. In the TAF condition, the pitch of the feedback voice was randomly shifted either up or down from the original pitch two or three times in each trial. The subjects were required to hold the pitch of the feedback voice constant by changing the pitch of original voice. In non-TAF condition, the pitch of the feedback voice was not modulated and the subjects just vocalized /a/ continuously. The contrast between TAF and non-TAF conditions revealed significant activations; the supramarginal gyrus, the prefrontal area, the anterior insula, the superior temporal area and the intraparietal sulcus in the right hemisphere, but only the premotor area in the left hemisphere. This result suggests that auditory feedback control of pitch is mainly supported by the right hemispheric network.

Automatic discriminative sensitivity inside temporal window of sensory memory as a function of time.

Neural representation of preceding sound-patterns stored in the human brain, as reflected by mismatch negativity (MMN) related to the automatic discriminative process, is restricted to a duration of 160-170 ms due to the short form of auditory sensory memory termed the temporal window of integration (TWI). To examine the temporal uniformity of deviation-sensitivity inside TWI of sensory memory, magnetic MMN (MMNm) responses were measured with a dual 37-channel magnetometer for complex sounds of 170 ms duration containing an omitted (silent) segment. Frequent standard stimuli (probability of 80%) consisted of five tone segments. Deviant stimuli were different from standard stimuli in that one of four segments was occasionally (probability of 5%) omitted and replaced by a silent segment. The stimulus duration of 170 ms was intended to correspond to the postulated duration of TWI. When the silent segment occurred later in deviant stimulus, the MMNm peak amplitude was attenuated and MMNm peak latency, measured from the onset of each silent segment, was delayed. Thus, automatic deviation-detection sensitivity declines nonlinearly toward the end of TWI in auditory sensory memory. In the second experiment, two types of deviant stimuli, which differed from each other only in the period after the occurrence of the silent segment, elicited MMNm with the same peak latency but with a different peak amplitude. Thus, mismatch process is triggered at the moment of change but still lasts after the detection of deviation. In other words, both standard and deviant stimuli are treated as a unitary event within a TWI.

Organizing sound sequences in the human brain: the interplay of auditory streaming and temporal integration.

The present study examined the relationship between two of the early brain processes of sound organization: auditory streaming and the temporal window of integration (TWI). Presented at a fast stimulus delivery rate, two tones alternating in frequency are perceived as separate streams of high and low sounds. However, when two sounds are presented within a ca. 200 ms temporal window, they are often processed as a single auditory event. Both stream segregation and temporal integration occur even in the absence of focused attention as was shown by their effect on the mismatch negativity (MMN) event-related potential. The goal of the present study was to determine the precedence between these two sound organization processes by using the stimulus-omission MMN paradigm. Infrequently omitting one stimulus from a homogeneous tone sequence only elicits an MMN when the stimulus onset asynchrony separating successive tones is shorter than 170 ms. This demonstrates the effect of the TWI. Magnetic brain responses elicited by infrequent stimulus omissions appearing in a sequence of two alternating tones were recorded. The magnetic MMN was elicited by tone omission when the alternating tones formed a single stream (with no or only small frequency separation between the two tones) but not when separate high and low streams emerged in perception (large frequency separation between the two alternating tones). This result shows that auditory streaming takes precedence over the processes of temporal integration.

Epsin binds to the EH domain of POB1 and regulates receptor-mediated endocytosis.

POB1 has been identified as a RalBP1-binding protein and has the Eps15 homology (EH) domain. The EH domain-containing proteins have been suggested to be involved in clathrin-dependent endocytosis. To clarify the function of POB1, we purified a protein which binds to the EH domain of POB1 from bovine brain cytosol and identified it as Epsin, which is known to bind to the EH domain of Eps15. Epsin has three Asn-Pro-Phe (NPF) motifs in the C-terminal region, which are known to form the core sequence for the binding to the EH domain. The EH domain of POB1 interacted directly with the region containing the NPF motifs of Epsin. Expression of Epsin in CHO-IR cells inhibited internalization of insulin although it affected neither insulin-binding nor autophosphorylation activities of the insulin receptor. Taken together with the observations that Epsin is involved in internalization of the receptors for epidermal growth factor and transferrin, these results suggest that Epsin is a binding partner of POB1 and their binding regulates receptor-mediated endocytosis.

Structure of the auditory evoked magnetic fields during sleep.

We studied the effects of sleep on auditory evoked magnetic fields following pure tone stimulation applied to the right ear of 10 healthy normal volunteers to investigate the changes in the processing of auditory perception in the primary auditory cortex. Dual 37-channel biomagnetometers were used to record auditory evoked magnetic fields over the bilateral temporal lobes in response to presented tones. Auditory evoked magnetic fields were compared for three stimulus frequencies (250, 1000 and 4000 Hz) and three sleep stages (awake state, sleep stages 1 and 2). Four main components, M50, M100, M150 and M200, were identified with latencies of approximately 50, 100, 150 and 200 ms, respectively. The latency of each component had a tendency to be prolonged with the depth of sleep stage in all frequencies. The amplitude ratios of the early-latency components (M50 and M100) showed a tendency of reduction compared with the same components in the awake state. By contrast, the amplitude ratios of the long-latency components (M150 and M200) were significantly enhanced with an increase in the sleep stage compared with the same components in the awake state. The equivalent current dipoles of all components in all conditions were detected at the superior temporal cortex (the primary auditory cortex). As for the changes in the equivalent current dipole location of each component, the equivalent current dipole was detected in the more posterior and medial region in responses to the high-frequency tone (1000 and 4000 Hz) compared with those to 250 Hz tone stimulation. Although the equivalent current dipoles of the early-latency components (M50 and M100) were in regions more anterior and superior compared to those in the awake state, there was no consistent tendency of changes in equivalent current dipole locations between each sleep stage in the late-latency components (M150 and M200). These findings are probably due to the difference in generating mechanisms between the early- and late-latency components.

A 21-aminosteroid, U-74006F, attenuates endotoxin-induced lung injury in awake sheep.

The purpose of the present study was to examine the efficacy of U-74006F, a 21-aminosteroid, on lung dysfunction induced by endotoxaemia in awake sheep with lung lymph fistula and haemodynamic monitoring. We measured pulmonary haemodynamics, lung lymph balance, circulating leucocyte count, arterial blood gas tensions, and levels of thromboxane (Tx) B2 and 6-keto-prostaglandin (PG) F1 alpha in plasma and lung lymph. We performed two experiments. In experiment 1 (n = 6), we intravenously infused Escherichia coli lipopolysaccharide endotoxin (1 microgram/kg) over 30 min and observed the parameters over 5 h. In experiment 2 (n = 6), we pretreated sheep with an intravenous bolus of U-74006F (2 mg/kg) 30 min before the infusion of endotoxin in the same manner of experiment 1, and continuously infused U-74006F (0.5 mg/kg per h) over 5 h after the bolus during the experiment. The U-74006F significantly suppressed the early pulmonary hypertension, the late increase in pulmonary permeability and the elevations of TxB2 and 6-keto-PGF1 alpha levels in plasma and lung lymph during the early period following endotoxaemia, although the compound did not change the time course of leucocytopenia and hypoxaemia. These findings suggest that the administration of U-74006F attenuates the lung dysfunction induced by endotoxaemia in awake sheep.

Lecithinized superoxide dismutase attenuates phorbol myristate acetate-induced injury in isolated dog lung.

Lecithinized superoxide dismutase, a lecithin derivative bound to recombinant human CuZn superoxide dismutase, has a higher affinity for cells such as polymorphonuclear leukocytes and endothelial cells than recombinant human CuZn superoxide dismutase has. We determined the protective effects of lecithinized superoxide dismutase on the increased microvascular permeability induced by phorbol myristate acetate (PMA) in isolated dog lungs. Microvascular permeability was assessed by the capillary filtration coefficient (Kf,c) and solvent drag reflection coefficient (sigma(f)). PMA (13.3 microg) increased microvascular permeability, as evidenced by an increase in Kf,c and the small sigma(f) value. Lecithinized superoxide dismutase at both low (4800 U) and high doses (48,000 U) inhibited the PMA-induced increase in Kf,c, but only the high dose of lecithinized superoxide dismutase attenuated the decrease in sigma(f). Recombinant human CuZn superoxide dismutase did not affect the PMA-induced increase in vascular permeability at either a low (4800 U) or a high dose (48,000 U). These findings suggest that lecithinized superoxide dismutase has a protective effect against oxygen radical-induced lung injury in isolated dog lungs.

A new substance (Yoshixol) with an interesting antibiotic mechanism from wood oil of Japanese traditional tree (Kiso-Hinoki), Chamaecyparis obtusa.

1. A neutral wood oil was extracted from Chamaecyparis obtusa (Kiso-Hinoki), which has been trusted nationally and preserved historically in the central part of Japan (Kiso, Nagano). 2. Hinokitiol, or thujaplicin (C10H12O2), which has been believed to exist in Cupressaceae, was not found in this neutral wood oil. Some differences between the extracting processes of the natural products are discussed. 3. A new chemical substance (Yoshixol, 4,4-dimethyl-6-methylene-2-cyclohexen-1-one) was simulated by several criteria (details in the text) as a major candidate of the neutral wood oil from Chamaecyparis obtusa. Thus, Yoshixol was newly synthesized. 4. The antibiotic effects of hinokitiol, the neutral wood oil and Yoshixol on methicillin-resistant Staphylococcus aureus (MRSA) were examined bacteriologically and morphologically. 5. All of the aforementioned three test materials showed complete antibiotic effects on MRSA by the bacteriological examination. However, the morphological findings showed entirely different aspects of cell death. 6. Hinokitiol caused an aggregative, degenerative and/or necrotic aspect, but the neutral wood oil and Yoshixol produced characteristic aspects: separation of contacted cells, blebbing, bugging-like eruption, formation of granules and an extensive reduction of individual cell size of MRSA. 7. Yoshixol was able to enhance those antibiotic effects on MRSA distinctly more than the neutral wood oil. 8. Yoshixol also showed a strong antibiotic effect on Escherichia coli, Mycobacterium chelonei, Pseudomonas aureginosa and Candida albicans. Morphological observations of those bacilli after Yoshixol revealed characteristic aspects of separation of contacted cells, bugging-like swelling, granulation, ballooning and reduction of cell size. 9. A possible mechanism of Yoshixol is discussed in regard to a molecular orbital theory on the basis of its electron orbits and to a thermodynamic interaction with the prokaryotic cell membrane. On the basis of the molecular properties of Yoshixol, future biological interests and possible biological effects of Yoshixol are suggested.

Apoptosis-like (possible quantum thermodynamic) cell death induced by Yoshixol and wood oil of Chamaecyparis obtusa (Kiso-Hinoki) on HeLa cell.

1. We report on the cytotoxic effects of neutral wood oil extracted from Chamaecyparis obtusa (Kiso-Hinoki) and of the newly synthetized substance Yoshixol (4,4-dimethyl-6-methylene-2-cyclohexen-1-one) on cultured HeLa cells. 2. The neutral wood oil produced cell death, led to the formation of granules, which were connected with fibrous networks, and reduced cell size. 3. Yoshixol caused a separation of cells, granulation, formation of high-density materials (probably apoptotic body), and reduction of cell size. 4. DNA fragmentation on the electrophoresis was observed with Yoshixol. A low-molecular-weight smear band appeared in the supernatant after treatment with the neutral wood oil. Neither treatment showed higher lactate dehydrogenase (LDH) activity in the culture medium than seen with ethanol as a control. 5. These findings suggest that both the neutral wood oil and Yoshixol have a similar cytotoxic mechanism, reducing cell size and producing a granulation (fragmentation) of eukaryotic cells. 6. Yoshixol may be a potent antitumor agent that induces apoptotic-like cell death. This possible mechanism is discussed.

Effects of movement and movement imagery on somatosensory evoked magnetic fields following posterior tibial nerve stimulation.

We examined the "gating" effects caused by active and passive movements of toes and by "movement imagery" (mental moving of the toe without actual movements) on somatosensory evoked magnetic fields (SEFs) following stimulation of the posterior tibial nerve in normal subjects. Active and passive movements significantly attenuated the short- and middle-latency cortical components (P < 0.001) with no latency change, and the effects of the active movements were larger than those of the passive movements. In contrast, the subsequent long-latency component with a latency of about 100 ms was enhanced only by the active movements. Therefore, both centrifugal and centripetal mechanisms should be considered. The gating effects by movements on all components may occur in the primary sensory cortex (SI) in the hemisphere contralateral to the stimulated nerve, because all of the equivalent current dipoles (ECDs) of the components in the "control" and each "interference" waveform were located there. Active movements of the toes contralateral to the stimulated nerve caused no significant gating effect. The short-latency components were not consistently changed by "movement imagery", but the middle- and long-latency components were enhanced. Their ECDs were located in the SI contralateral to the stimulated nerve and in the SII in bilateral hemispheres. Therefore, we speculated that brain responses to somatosensory stimulation, particularly components generated in SII, were affected by volitional changes.

Japanese dreams: culture and cosmology.

Attitudes to dream evaluation vary depending on culture. Dreams are considered important, real, and public in some cultures, but absurd, irrational and personal in others. Japan has its own history of dreaming, which can be well reconstructed due to rich sources of archeological and documentary material. In this paper dream evolution in Japan is described. Phase 1 is the prehistoric Jomon period, where people believed dreams were part of reality. From Phase 2, the sophisticated philosophies of Confucianism, Buddhism and Taoism were introduced and changed the social and mental system of Japan in phase 3. At phase 4, the amalgamation of local and alien cultures occurred and supernatural beliefs prevailed. In this society dreams played a very important role. Phase 5 is the period when the Samurai class ruled Japan. The pragmatic thinking of the Samurai succeeded in fostering good preconditions for the receipt of scientific Western culture in phase 6. The importance of dreams in Japan evolved in such a way. However, the elements of each phase continued and accumulated similar layers. Thus, a majority of the phases seemed to retain animism from the Jomon period.

Refractoriness of eucapnic hyperventilation-induced bronchoconstriction in rabbits.

The mechanism of refractoriness in bronchoconstriction after repeated hyperventilation was investigated in 18 sensitized rabbits. Rabbits were separated into three groups: an untreated control group (n = 7), a cimetidine-treated group (n = 6), and an indomethacin-treated group (n = 5). After anesthetization, hyperventilation was performed for 15 min (120 breaths/min, 7 ml/kg tidal volume) with dry air containing 5% CO2. Total lung resistance (RL) and dynamic compliance (Cdyn) were measured before (baseline) and after hyperventilation challenge. After RL and Cdyn had returned to baseline values, the hyperventilation challenge was repeated. In the control group maximal increase in percent RL (max %RL) was 49 +/- 9% after the first challenge, but 16 +/- 4% after the second challenge, indicating refractoriness. A similar tendency was observed in percent Cdyn. In the cimetidine- and indomethacin-treated groups, max %RL were 42 +/- 3% and 60 +/- 15% after the first challenge, and 35 +/- 8% and 60 +/- 7% after the second challenge, respectively, indicating no refractoriness. These results suggest that the H2-receptor and bronchodilating prostanoids play an important role in producing the refractoriness to bronchoconstriction observed in sensitized rabbits after repeated hyperventilation.

Chronic motor cortex stimulation in patients with thalamic pain.

Analysis of the authors' experience over the last 10 years has indicated that excellent pain control has rarely been obtained by thalamic relay nucleus stimulation in patients with thalamic pain. In the present study, 11 patients with thalamic pain were treated by chronic stimulation of the precentral gyrus. In eight patients (73%), the stimulation system was internalized since excellent pain control was achieved during a 1-week test period of precentral gyrus stimulation. In contrast, no clear effect was noted or the original pain was even exacerbated by postcentral gyrus stimulation. The effect of precentral stimulation was unchanged in five patients (45%) for follow-up periods of more than 2 years. In the remaining three patients, the effect decreased gradually over several months. This outcome was significantly better than that obtained in an earlier series tested by the authors with thalamic relay nucleus stimulation (p < 0.05). The pain inhibition usually occurred at intensities below the threshold for production of muscle contraction (pulse duration 0.1 to 0.5 msec, intensity 3 to 8 V). When good pain inhibition was achieved, the patients reported a slight tingling or mild vibration sensation during stimulation projected in the same area of distribution as their pain. The authors discuss the possibility that, in deafferentation pain, sensory neurons below the level of deafferentation cannot exert their normal inhibitory influences toward deafferented nociceptive neurons because of the development of aberrant connections. Thus, while stimulation of the first- to third-order sensory neurons at the level of the thalamic relay nucleus or below cannot bring about good pain inhibition in patients with thalamic pain, activation of hypothetical fourth-order sensory neurons through precentral stimulation may be able to inhibit deafferented nociceptive neurons within the cortex. None of the patients developed either observable or electroencephalographic seizure activity.

Characterization and modification of brain activity with deep brain stimulation in patients in a persistent vegetative state: pain-related late positive component of cerebral evoked potential.

A series of eight patients in a persistent vegetative state (PVS) were subjected to chronic deep brain stimulation (DBS) for the purpose of promoting recovery from the PVS. The characteristics of the brain activity in these patients were evaluated from the late positive component of the cerebral evoked potential in response to painful stimuli (pain-related P250). While any neurological scoring system for the comatose state includes evaluations of motor reactions to painful stimuli, the pain-related P250 is unique in terms of its ability to assess the cortical responsiveness to painful stimuli directly and quantitatively without involving functions of the motor system. It was found that the pain-related P250 was more or less depressed in patients in a PVS. It was repeatedly demonstrated in four patients, however, that the pain-related P250 could be transiently increased by preceding stimulation of the mesencephalic reticular formation. Furthermore, a persistent increase in the pain-related P250 was produced in these four patients following chronic DBS of the mesencephalic reticular formation or nonspecific thalamic nuclei for more than 6 months, and this was correlated with the clinical improvements. These results imply that responsiveness at the cortical level to pain is depressed in the PVS. It also appears that some fraction of the depression may, however, be functionally produced and potentially reversible.

Treatment of thalamic pain by chronic motor cortex stimulation.

All forms of therapy, including chronic stimulation of the thalamic relay nucleus, can provide satisfactory pain control in only 20%-30% of cases of thalamic pain syndrome. In order to develop a more effective treatment for thalamic pain syndrome, we investigated the effects of stimulation of various brain regions on the burst hyperactivity of thalamic neurons recorded in cats after deafferentiation of the spinothalamic pathway. Complete, long-term inhibition of the burst hyperactivity was induced by stimulation of the motor cortex. Based on this experimental finding, we treated seven cases of thalamic pain syndrome by chronic motor cortex stimulation employing epidural plate electrodes. Excellent or good pain control was obtained in all cases without any complications or side effects. During the stimulation, an increase in regional blood flow of the cerebral cortex and thalamus, a marked rise in temperature of the painful skin regions, and improved movements of the painful limbs were observed. These results suggest that thalamic pain syndrome can be most effectively treated by chronic motor cortex stimulation.

Chronic motor cortex stimulation for the treatment of central pain.

Twelve patients with deafferentation pain secondary to central nervous system lesions were subjected to chronic motor cortex stimulation. The motor cortex was mapped as carefully as possible and the electrode was placed in the region where muscle twitch of painful area can be observed with the lowest threshold. 5 of the 12 patients reported complete absence of previous pain with intermittent stimulation at 1 year following the initiation of this therapy. Improvements in hemiparesis was also observed in most of these patients. The pain of these patients was typically barbiturate-sensitive and morphine-resistant. Another 3 patients had some degree of residual pain but considerable reduction of pain was still obtained by stimulation. Thus, 8 of the 12 patients (67%) had continued effect of this therapy after 1 year. In 3 patients, revisions of the electrode placement were needed because stimulation became incapable of inducing muscle twitch even with higher stimulation intensity. The effect of stimulation on pain and capability of producing muscle twitch disappeared simultaneously in these cases and the effect reappeared after the revisions, indicating that appropriate stimulation of the motor cortex is definitely necessary for obtaining satisfactory pain control in these patients. None of the patients subjected to this therapy developed neither observable nor electroencephalographic seizure activity.

[The efficacy of temporary retention chemotherapy of the treatment of polyps in the remnant rectum of familial polyposis after total colectomy and ileorectostomy--a case report].

A case of familial polyposis is reported. The patient was a 24-year-old woman on whom total colectomy followed by ileorectostomy had been performed. However, there were multiple polyps remaining in the remnant rectum. For the treatment of these residual polyps, a new chemotherapeutic method known as Temporary Retention Chemotherapy (TRC), originally devised by us for the treatment of advanced gastric cancer, was applied. A balloon catheter was inserted and fixed into the rectum via the anus for the treatment of the rectal tumors. Through the catheter, high-dose 5-fluorouracil (5-FU) solution was injected into the rectum and retained there for one hour before being discarded. During the therapy, the patient was asked to change her position of recumbency at certain intervals, so that the 5-FU solution could act evenly on the lesions in question. This therapy was repeated twice a week, and followed by routine endoscopic studies. A total dose of 5,700 mg of 5-FU was necessary for obtaining a complete response of the remnant lesions. 6 months later, 4 polyps were found, and TRC was again applied, resulting in disappearance of the polyps again after the therapy. So far, no side-effect have been noted as a result of this therapy. She is currently still alive without any residual polyps, carcinoma or metastasis 6 years after the operation.