Hemispheric lateralization in the cortical motor preparation for human vocalization.

To investigate the cortical information processing during the preparation of vocalization, we performed transcranial magnetic stimulation (TMS) over the cortex while the subjects prepared to produce voice in response to a visual cue. The control reaction time (RT) of vocalization without TMS was 250-350 msec. TMS prolonged RT when it was delivered up to 150-200 msec before the expected onset of voice (EOV). The largest delay of RT was induced bilaterally over points 6 cm to the left and right of the vertex (the left and right motor areas), resulting in 10-20% prolongation of RT. During the early phase of prevocalization period (50-100 msec before EOV), the delay induced over the left motor area was slightly larger than that induced over the right motor area, whereas, during the late phase (0-50 msec before EOV), it was significantly larger over the right motor area. Bilateral and simultaneous TMS of the left and right motor areas induced delays not significantly different from that induced by unilateral TMS during the early phase, but induced a large delay well in excess of the latter during the late phase. Thus, during the cortical preparation for human vocalization, alternation of hemispheric lateralization takes place between the bilateral motor cortices near the facial motor representations, with mild left hemispheric predominance at the early phase switching over to robust right hemispheric predominance during the late phase. Our results also suggested involvement of the motor representation of respiratory muscles and also of supplementary motor cortex.

Right ventricular filling detected by pulsed Doppler echocardiography during the convalescent stage of inferior wall acute myocardial infarction.

To evaluate right ventricular (RV) diastolic function in patients with inferior wall acute myocardial infarction (AMI), flow velocity patterns of the RV inflow tract were studied in patients with anterior AMI (n = 32), inferior AMI (n = 32) and angina pectoris without left ventricular asynergy (n = 10) using pulsed Doppler echocardiography. Doppler examinations were performed at least 4 weeks after the attack. Twenty-seven healthy persons served as control subjects. Three Doppler variables were measured at the RV inflow tract: the ratio of the late diastolic peak flow velocity due to atrial contraction to the rapid filling peak flow velocity in early diastole (A/E) and the acceleration time and deceleration time of the RV rapid filling wave. A/E in patients with inferior AMI (1.01 +/- 0.24, mean +/- standard deviation) was significantly greater than in those with anterior AMI (0.80 +/- 0.16, p less than 0.001) and angina pectoris (0.79 +/- 0.17, p less than 0.01) and in normal subjects (0.70 +/- 0.17, p less than 0.001). A/E in patients with inferior AMI correlated with the ratio of left ventricular to RV end-diastolic pressure (r = -0.60, p less than 0.05). A/E in inferior AMI with relatively high RV end-diastolic pressure (more than 8 mm Hg, n = 8) was significantly greater than that in those with normal pressure (8 mm Hg or less, n = 9). A/E in patients with proximal right coronary artery occlusion was significantly greater than that in those with distal occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of pulmonary arterial pressure in adults by pulsed Doppler echocardiography.

Doppler echocardiography was used to estimate pulmonary artery (PA) pressure in 45 adult patients with various kinds of heart disease and the patterns were compared with those of 32 normal control subjects. Doppler signals obtained in the right ventricular (RV) outflow tract just proximal to the pulmonary valve and electrocardiogram were recorded simultaneously. Doppler velocity time intervals were measured as follows: RV preejection period, acceleration time from the onset of the RV ejection flow velocity to the peak, and RV ejection time. Thirty patients had PA hypertension and 16 patients had a low cardiac index. The best correlation with PA pressure was achieved by the RV preejection period/acceleration time index (r = 0.89 vs mean pressure). Sensitivity and specificity for predicting PA hypertension were 93% and 97%, respectively. Acceleration time correlated best with the logarithm of PA mean pressure (r = 0.88). Patients were separated into 2 groups according to cardiac index. In those patients with a cardiac index of less than 2.5 liters/min/m2, both RV preejection period/acceleration time and acceleration time were significantly correlated with PA mean pressure (r = 0.87) and log (PA mean pressure) (r = -0.87), respectively. However, the slope of the regression line for acceleration time and log (PA mean pressure) was significantly steeper than that for patients with a cardiac index of greater than or equal to 2.5 liters/min/m2 (p less than 0.05), whereas the relation between RV preejection period/acceleration time and PA mean pressure in the 2 groups could not be differentiated statistically from each other. Other intervals and ratios were less quantitative because of late systolic turbulent flow and individual variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Predominant activation of I1-waves from the leg motor area by transcranial magnetic stimulation.

We performed transcranial magnetic stimulation (TMS) to elucidate the D- and I-wave components comprising the motor evoked potentials (MEPs) elicited from the leg motor area, especially at near-threshold intensity. Recordings were made from the tibialis anterior muscle using needle electrodes. A figure-of-eight coil was placed so as to induce current in the brain in eight different directions, starting from the posterior-to-anterior direction and rotating it in 45 degrees steps. The latencies were compared with those evoked by transcranial electrical stimulation (TES) and TMS using a double cone coil. Although the latencies of MEPs ranged from D to I3 waves, the most prominent component evoked by TMS at near-threshold intensity represented the I1 wave. With the double cone coil, the elicited peaks always represented I1 waves, and D waves were evoked only at very high stimulus intensities, suggesting a high effectiveness of this coil in inducing I1 waves. Using the figure-of-eight coil, current flowing anteriorly or toward the hemisphere contralateral to the recorded muscle was more effective in eliciting large responses than current flowing posteriorly or toward the ipsilateral hemisphere. The effective directions induced I1 waves with the lowest threshold, whereas the less effective directions elicited I1 and I2 waves with a similar frequency. Higher stimulus intensities resulted in concomitant activation of D through I3 waves with increasing amount of D waves, but still the predominance of I1 waves was apparent. The amount of I waves, especially of I1 waves, was greater than predicted by the hypothesis that TMS over the leg motor area activates the output cells directly, but rather suggests predominant transsynaptic activation. The results accord with those of recent human epidural recordings.

Granulocyte-colony stimulating factor stimulates immunoreactive endothelin-1 release from cultured bovine endothelial cells.

We examined the effect of human recombinant granulocyte-colony stimulating factor (G-CSF) on the release of immunoreactive endothelin-1 (ET-1) from cultured bovine vascular endothelial cells. G-CSF dose dependently (10(-8)-10(-6) M) increased the release of immunoreactive ET-1 as a function of time under a serum-free condition. Coaddition of G-CSF and thrombin induced an additive effect on immunoreactive ET-1 release. Neither Ca2+ channel antagonist nor cyclooxygenase inhibitor affected immunoreactive ET-1 release stimulated by G-CSF. These results suggest that G-CSF, in addition to its effect on granulocyte progenitors, has a direct effect on vascular endothelium to induce the release of immunoreactive ET-1.

Somatosensory evoked high-frequency oscillation in Parkinson's disease and myoclonus epilepsy.

AIM: A high-frequency oscillation in the range of 600-900 Hz has been shown to be a component of the somatosensory evoked potential (SEP) in humans. In the present communication, we studied these oscillation potentials in two neurological disorders. SUBJECTS AND METHODS: Subjects were 20 healthy volunteers, 17 patients with Parkinson's disease (PD) and 3 with myoclonus epilepsy (ME). Median nerve SEPs were recorded using filters set at 0.5 and 3000 Hz. Several peaks of oscillation were obtained by digitally filtering raw SEPs from 500 to 1000 Hz, and their amplitudes and onset latencies were measured. RESULTS: In normal subjects, several oscillation potentials were observed at the latency of 0 to 8 ms after the onset of N20. In PD patients, the oscillation potentials at normal latencies were significantly larger than those of normal subjects. Moreover, in 7 of 17 PD patients, they were extremely enlarged (>mean +/- 3 SD of normal values). In contrast, in patients with ME, abnormally enlarged oscillation potentials were seen at longer latencies (7-14 ms) in spite of normal-sized early oscillation potentials. Magnetoencephalographic analyses showed that any oscillation potentials originated from the primary sensory cortex. CONCLUSIONS: There are at least two mechanisms for producing the oscillation potentials of SEP. Those around N20 have some relation with the basal ganglia function and are enlarged in PD patients, the others around P25-N33 are enhanced in ME patients.

Input-output organization of the foot motor area in humans.

OBJECTIVE: A well-organized input-output relation similar to that of the monkey motor cortex has been demonstrated in the human hand motor area (Terao Y, Ugawa Y, Uesaka Y, Hanajima R, Gemba-Shimizu K, Ohki Y, Kanazawa I. Input-output organization in the hand area of the human motor cortex, Electroenceph clin Neurophysiol 1995;97:375-381). The aim of this study is to investigate the input-output organization of the human foot motor area. METHODS: We studied the effect of tactile stimuli given to the toe tip on the sizes of following responses; motor evoked potentials (MEPs) elicited by transcranial magnetic or electrical stimulation (TMS or TES) over the motor cortex and magnetic stimulation at the foramen magnum level. RESULTS: Air stimuli applied to the toe tip facilitated magnetically evoked MEPs of mainly the muscle attached to that toe, although a less prominent facilitation was also noted in muscles attached to the adjacent toes. Neither responses evoked by TES, nor those by stimulation at the foramen magnum level, were affected by air stimuli. These results suggest that the observed facilitatory effect occurs at the cortical level. CONCLUSION: A fairly well-organized input-output relation is present also in the foot motor area in humans, although the facilitatory effect is not so topographically restricted as is noted for the hand motor area.

The human hand motor area is transiently suppressed by an unexpected auditory stimulus.

OBJECTIVE: To study the effect of a loud auditory stimulus on the excitability of the human motor cortex. METHODS: Ten normal volunteers participated in this study. The size of responses to transcranial magnetic or electrical cortical stimulation (TMS or TES) given at different times (ISIs) after a loud sound were compared with those to TMS or TES alone (control response). Different intensities and durations of sound were used at several intertrial intervals (ITIs). In addition, we examined how the presence of a preceding click modulated the effect of a loud sound (prepulse inhibition). The incidence of startle response evoked by various stimuli was also studied. RESULTS: A loud auditory stimulus suppressed EMG responses to TMS when it preceded the magnetic stimulus by 30-60 ms, whereas it did not affect responses to TES. This suggests that the suppression occurred at a cortical level. Significant suppression was evoked only when the sound was louder than 80 dB and longer than 50 ms in duration. Such stimuli frequently elicited a startle response when given alone. The effect was not evoked if the ITI was 5 s, but was evoked when it was longer than 20 s. A preceding click reduced the suppression elicited by loud sounds. CONCLUSIONS: Auditory stimuli that produced the greatest effect on responses to TMS had the same characteristics as those which yielded the most consistent auditory startle. We suggest that modulation of cortical excitability occurs in parallel with the auditory startle and both may arise from the same region of the brain-stem.

Physiological analyses of a patient with extreme widening of Virchow-Robin spaces.

We report on a 60-year-old woman with extreme widening of Virchow-Robin spaces who showed neither neurological symptoms nor signs. Magnetic resonance imagings (MRIs) of her brain disclosed multiple abnormalities located along the perforating medullary arteries in the white matter. Central sensory and motor conduction studies (sensory evoked potentials (SEPs) and magnetic stimulation) showed no conduction delays and several modulatory inputs normally influenced the motor and sensory cortical excitability, as expected from clinical features. These physiological analyses confirmed the functional integrity of the central sensory and motor systems, even though imaging studies showed seemingly serious abnormalities.

A single motor unit recording technique for studying the differential activation of corticospinal volleys by transcranial magnetic stimulation.

The purpose of this method is to establish a single motor unit recording technique to study the differential activation of corticospinal volleys by various types of transcranial magnetic stimulation (TMS). TMS is performed with various coil orientations over the hand or leg motor areas and surface EMG, and single motor unit recordings are made either from the studied hand or leg muscle. Transcranial electrical stimulation (TES) is also performed over the motor cortex as well as at the foramen magnum level to determine the latency of D waves. The intensity of stimulation is set just above the motor threshold for each type of stimulation. This method makes it possible to activate some I volleys (especially I1 and I3 waves) preferentially, if not selectively, from the hand and leg motor areas. The obtained results accord well with recent epidural recording studies, which lends support to the validity of this method.

Endothelin-1- and endothelin-3-induced vasorelaxation via common generation of endothelium-derived nitric oxide.

The vasorelaxant effects by endothelin-1 (ET-1) and endothelin-3 (ET-3), and their mechanisms of action were studied in isolated porcine pulmonary arterial strips. ET-1 and ET-3 dose-dependently (10(-9) - 10(-8) M) relaxed vascular strips precontracted with norepinephrine only in the presence of endothelium. The maximal vasorelaxant effect by ET-1 was about 70% of that by ET-3. The ET-1- and ET-3- induced vasorelaxation was blocked by NG-nitro-L-arginine, an inhibitor of nitric oxide synthesis, and methylene blue, an inhibitor of soluble guanylate cyclase. The present data suggest that vascular smooth muscle relaxation induced by ET-1 and ET-3 is mainly ascribed to synthesis and release of nitric oxide from L-arginine in endothelium.

[Scinti-angiographic investigation of aortic dissection (author's transl)]. / Szintiagiographische Analyse einer Aortadissektion.

We perform scinti-angiography regularly in suspected cases of dissecting aneurysms. In our experience, the dissection is well demonstrated by this method. In correctly selected cases, scinti-angiography is a method which is well tolerated by the patient and which carries very little risk, since the complications due to contrast media are absent.

MHV-induced fatal peritonitis in mice lacking IFN-gamma.

IFN-gamma gene was disrupted by homologous recombination in A3-1 embryonic stem cells. Germinally transmitted chimeric mice were successfully obtained and backcrossed with C57BL/6 (B6) mice 5 or 6 times. Deficiency of IFN-gamma in homozygous mice was confirmed by northern blot analysis of spleen cells stimulated with phorbor esther and calcium ionophore and also by IFN-gamma production in the culture supernatant of spleen cells stimulated with the same reagents. B6 mice lacking IFN-gamma were infected intraperitoneally (ip) with 10(6) PFU of JHMV and monitored for their survival. Approximately 90% of the mice died at 50 days post-infection (pi) and the mean survival time was 28 days. Mice sacrificed at 3 weeks pi showed severe peritonitis accompanying the accumulation of a viscous fluid in the abdominal and thoracic cavities. Microscopically, the disease was characterized by disseminated granulomatous inflammation and exudative fibrinous serositis in the abdominal cavity. Infectious virus was isolated in most tissues including the liver, spleen, kidney, pancreas and lung during the experimental periods. The disease was not observed in wild-type or heterozygous littermates infected i.p. with JHMV. These results suggest that IFN-gamma plays a critical role in MHV infection in mice. This experimental model may provide a unique opportunity to address the pathogenesis of virus-induced peritonitis such as feline infectious peritonitis in cats.

Hemodynamic alterations in hemiplegic patients as a cause of edema in lower extremities.

The purpose of the study is to investigate the relationship between the hemodynamic change and the production of edema in the hemiplegic leg. This study was designed to compare the hemodynamics in the involved edematous leg with that in the unaffected non-edematous leg in hemiplegic patient using straingauge plethysmography and photo-plethysmography. Examinations were undertaken in 20 patients with hemiplegia. Arterial Inflow Ratio [healthy side; hemiplegic side (100/ml ml/min)]: 19.2 +/- 16.2; 27.6 +/- 23.4. Venous Distensitivity: 1.5 +/- 0.8; 1.9 +/- 1.0. Maximum Venous Outflow: 90.8 +/- 43.1; 120.0 +/- 52.9. Tissue Flow Ratio: 1.1 +/- 0.5; 1.6 +/- 0.6. The values for hemiplegic side were significantly higher than those for healthy side in all patients. It was confirmed by using photo-plethysmography that none of the patients had arterial obliterative disease. It was suggested that one of the causes of the production of edema in a hemiplegic limb was due to the dilated capillary vessels and congested lower extremity.

Role of CD4+ and CD8+ T cells in mouse hepatitis virus infection in mice.

Viral growth and histopathological changes in the liver after intraperitoneal infection with mouse hepatitis virus, strain JHM were compared among normal C57BL/6 mice, those depleted of CD4+ T cells, CD8+ T cells and both T cell subsets. Viral growth in mice depleted of CD4+ T cells increased slightly, but pathological changes resembled those in normal mice. In contrast, the hepatitis was exacerbated in mice depleted of CD8+ T cells and those depleted of both T cell subsets. These results suggest that CD8+ T cells play a key role although both T cell subsets are involved in protection against mouse hepatitis virus infection in mice.

Effect of increased systemic venous pressure on thoracic duct and peripheral lymph flow in dogs.

In congestive heart failure, lymph flow from the cannulated thoracic duct is greatly increased. However, there has been scant data on lymph flow in the intact lymphatic system with systemic circulatory congestion. In the present study, thoracic duct and peripheral lymph flow were qualitatively determined using heated cross-thermocouples in seven mongrel dogs. Central venous pressure was raised artificially by infusing large volumes of crystalloid solution equivalent to a maximum of 30% of body weight. Although both thoracic duct and peripheral lymph flow increased with an intact (closed) lymphatic system, the increase was notably less than with a transected (opened) cervical thoracic duct. With systemic circulatory congestion, cannulated thoracic duct lymph flow circumvents a major lymph impediment to lymph flow (i.e. high central venous pressure) and therefore considerably overestimates in vivo central lymph flow in this condition.

Generation of antiviral CD11ahigh T cells in CD4+ T cell-depleted mice and adult thymectomized mice after mouse hepatitis virus infection.

The mechanism of CD11ahighCD8+ T cell induction after mouse hepatitis virus infection, which has been suggested to play a key role in the elimination of infectious virus from the spleen in C57BL/6 mice, was studied. In CD4+ T cell-depleted mice, CD11ahighCD8+ T cells were induced in the spleen and spleen cells showed virus-specific cytotoxic T lymphocyte activity after mouse hepatitis virus infection. The same results were obtained in adult thymectomized mice. These results indicate that CD11ahighCD8+ T cells can be generated after mouse hepatitis virus infection in the absence of either CD4+ T cells or the thymus.

Characterization of T cells expanded in vivo during primary mouse hepatitis virus infection in mice.

After intraperitoneal infection with mouse hepatitis virus, strain JHM (JHMV), JHMV replicated in the spleen of C57BL/6 mice for a few days but cleared within a week. The acute viral clearance coincided with moderate expansion of CD8+T cells and modest expansion of CD4+T cells, and was impaired moderately in mice depleted of CD8+T cells and completely in mice depleted of both CD4+ and CD8+T cell subsets. Flow cytometric analysis showed that expression of cell surface markers on the spleen T cells changed during JHMV infection. CD8+T cells expressing increased amounts of CD11a, CD43, CD44 and CD49d, and those expressing decreased levels of T cell receptor alpha beta, CD8, CD45RB and L-selectin were expanded in the spleen after JHMV infection. However, they did not express CD11b, CD25 or NK1.1. They used highly heterogenous V beta chains for their T cell receptors. In addition to CD11ahighCD8+T cells, CD11ahighCD4+T cells were detected transiently after JHMV infection. The virus-specific cytotoxic T lymphocyte (CTL) activity was observed in both CD4+ and CD8+ spleen T cells from mice 7 days post-infection. The present study shows the dynamics of CD8+ and CD4+T cells in the spleen during JHMV infection in mice and suggests that CD11ahighT cells may be involved in JHMV clearance in vivo because their appearance was temporally correlated with T cell-mediated viral clearance in vivo and antiviral CTL activity in vitro.

Exercise training and the prevention of restenosis after percutaneous transluminal coronary angioplasty (PTCA).

To evaluate whether exercise training prevents the restenosis after percutaneous transluminal coronary angioplasty (PTCA), treadmill exercise with thallium-201 myocardial scintigraphy was performed at first and thirteenth week after PTCA in 18 patients with training and in 20 patients without training. Total treadmill exercise duration and maximal pressure rate product 13 weeks after PTCA increased significantly in the trained group, whereas there was no significant change in the untrained group. ST segment depression from the baseline did not change significantly in both groups. Myocardial perfusion obtained by Tl-201 scintigraphy improved significantly in the trained group, whereas there was no significant change in the untrained group. The restenosis rates at the third month after PTCA was 17% (3/18) in the trained group and 40% (8/20) in the untrained group. It is concluded that in patients with coronary artery disease, exercise training improves myocardial perfusion by preventing the progression of coronary artery stenosis after PTCA.

[123I-IMP SPECT findings of visual perseveration in a patient with old hemorrhage in the right occipital lobe].

We report a case of visual presevertation in a 67-year-old man. He had been well until 66 years of age when he had brain hemorrhage in the right occipital lobe. After an operation for removal of the hematoma, visual hallucination occurred and persisted for about 6 months. One year and a half later, he had a convulsive seizure and diphenylhydantoin was started. During the two weeks following the convulsion, he several times experienced episodes of visual preservation, visual hallucination and metamorphopsia. MRI revealed an old hemorrhage in the right occipital lobe. 123I-IMP SPECT demonstrated increase of cerebral blood flow of the right medial occipital lobe one day after the episode of visual perseveration and decrease about three weeks after the episode. The mechanism which causes visual perseveration still remains to be clarified. The findings of 123I-IMP SPECT of the present case suggest that visual perseveration may be generated by postictal transient functional excitation of the right occipital lobe.