PubMed Health⌕ Search

Biomedical subjects

A Nambu

Publications and source records attributed to A Nambu.

At least 55 records · Page 3Linked to original sources

Studies on integrative functions of the human frontal association cortex with MEG.

Our MEG studies on the human frontal association cortex are briefly reviewed. (1) The no-go potential was first found at go/no-go reaction-time hand movement task with discrimination between different colour light stimuli in the prefrontal cortex of monkeys. The potential was recorded in human subjects with EEG over the scalp, but its current dipoles could be localized only by use of MEG, in the dorsolateral part of the frontal association cortex in both cerebral hemispheres. The function for no-go decision and subsequent suppressor action was thus substantiated in the human frontal cortex. (2) Utterance of a short noun in Japanese was found to be initially preceded by an activity in the lower lateral part of the frontal lobe and then by that around the central sulcus. The area of the former, often in both hemispheres, appears to correspond to Broca's motor speech centre and that of the latter, always in both hemispheres, to correspond to the motor-somatosensory cortices. (3) Intensive and continuous concentration on mental calculation and some 'abstract' thinking for a few minutes were often associated with magnetic theta (5-7 Hz) wave bursts in the frontal part of the scalp. Dipole fitting suggested that the electrical current dipoles occur successively and scattered in wide areas of the frontal lobe on both sides. They are to be called "frontal mental theta wave", revealing dynamic and active participation of the frontal lobe in mental functions.

Adult↗

Direct projections from the orofacial region of the primary motor cortex to the superior colliculus in the macaque monkey.

Employing anterograde axonal tracing combined with intracortical microstimulation, we have revealed in the macaque monkey that the orofacial region of the primary motor cortex sends projection fibers to the deep layers of the superior colliculus. The terminal site of these projection fibers was almost localized to the lateral part of the intermediate gray layer at its rostral level, and spatially segregated from that of projection fibers arising from the frontal eye field. The results indicate the existence of a discrete tectal region related specifically to the control of orofacial movements.

Animals↗

Somatotopical projections from the supplementary motor area to the red nucleus in the macaque monkey.

Direct projections from the supplementary motor area (SMA) to the red nucleus were investigated in the Japanese monkey (Macaca fuscata). The anterograde tracer, horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP), was injected into various regions of the SMA after intracortical microstimulation mapping. After WGA-HRP injection into the orofacial, forelimb, or hindlimb region of the SMA, anterogradely labeled axon terminals were found, respectively, in the medial, intermediate, or lateral portion of the parvocellular part of the red nucleus, bilaterally with an ipsilateral predominance. The results indicate the clear somatotopical arrangement of corticorubral projections from the SMA.

Animals↗

Motor speech centres in the frontal cortex.

Activities of the frontal cortices in both cerebral hemispheres preceding utterance of a short word were recorded and analyzed with multichannel SQUID gradiometers. Light stimuli of two different colours of 500 ms duration were delivered in front of a subject at random time intervals and in irregular order of the different colours. The subject should respond to either of the stimuli by uttering a short word, e.g., 'en' [en] ('round' in Japanese) or another by a short simple voice without meaning as a word, e.g., 'e' [e]. The initial sounds of both voices are to be the same, i.e., 'e' [e] in these examples. The 37 gradiometers covering either the left or the right frontal-parietal part of the hemisphere recorded different magnetic fields between the word and the simple voice. Magnetic fields averaged 100 times at the onset of the stimuli revealed that the utterance of a word is preceded by significant magnetic field changes at a peak latency of 120-165 ms from the onset of light stimuli, whereas the utterance of a simple voice is not preceded by such changes. At a peak latency of 160-190 ms, about 20-40 ms before the start of perioral EMGs, both the utterances are commonly preceded by magnetic field changes. Dipole fittings based on these magnetic fields suggest that the earlier magnetic fields reflect electrical activities in the ventral lateral part of the frontal association area, usually in both left and right hemispheres, and that the later fields represent those in the sensorimotor area in both the hemispheres. That part of the frontal association area appears to be the centre for organizing words to speak and to correspond possibly to the Broca's speech area.

Adult↗

Mechanism of hypertension induced by chronic inhibition of nitric oxide in rats.

In order to clarify the mechanism of hypertension induced by a nitric oxide (NO) synthase inhibitor, L-NG-nitro-L-arginine (LNNA), metabolites of NO, catecholamines, and hemodynamic parameters were measured during 7 days of oral administration of LNNA in rats. Control rats received either L-arginine (L-Arg) or the vehicle. systolic blood pressure, measured by the tall-cuff method was elevated throughout the period of LNNA administration, but that in the two control groups was not influenced by treatment. Heart rate decreased on the second day only in LNNA-treated rats. Although L-Arg treatment had no influence, LNNA markedly decreased the plasma level and the urinary excretion of nitrate ions (NO-3). Urinary excretion of noradrenaline was significantly decreased on the second day of LNNA administration and returned to the control level thereafter. When hemodynamic changes were measured by using radioactive microspheres, LNNA was found to increase blood pressure by markedly increasing total peripheral resistance. Cardiac output was decreased by LNNA. L-Arg, again, did not influence the hemodynamic variables as compared with the vehicle control group. The regional vascular resistance index was increased by LNNA in many tissues and organs, except the brain and the heart. Regional blood flow, on the other hand, was significantly decreased only in the liver and skin by LNNA. The marked reduction in NO3- in urine by LNNA-treatments may indicate that the measured NO3- is exclusively of endogenous origin, and that inhibition of NO production causes elevation of blood pressure by constricting peripheral arteries. Sympatholytic responses by the baroreceptor reflex were thereby evident only on the second and the third days, which was indicated by bradycardia and suppression of noradrenaline excretion into urine. These results indicate that the inhibition of NO synthase actually decreases production of endogenous NO, and that the hypertension caused by decreases in NO production is due to elevation of total peripheral vascular resistance.

Animals↗

[Clinical studies of spermatogenic damage in patients with testicular cancer].

We investigated the spermatogenic function of patients with testicular cancer, and the influences of anti-cancer chemotherapy on testicular function in these patients. Fifty-one patients with testicular cancer were selected for evaluation of their testicular function, including spermatogenesis and endocrinological function, before and after chemotherapy with anti-cancer agents. Before chemotherapy with anti-cancer agents, 22 of 49 patients (44.8%) had a sperm concentration of less than 20 x 10(6)/ml, and 8 patients (16.3%) showed azoospermia. The mean sperm concentration of the patients with testicular cancer was 29.0 x 10(6)/ml before therapeutic chemotherapy with anti-cancer agents, but within 3 months after chemotherapy, it decreased to 3.86 x 10(6)/ml (p < 0.01). Fifteen of 19 patients (73.7%) were revealed to have azoospermia. Damage to spermatogenesis became more severe with the number of chemotherapy treatment. No patients had a detectable sperm count at the completion of 3 or more courses of chemotherapy. But some patients who received 3 courses or more of chemotherapy showed recovered sperm counts after 2 or more years. Thus, a lack of sperm after chemotherapy for cancer did not necessarily indicate inability to recover spermatogenesis over 2 years after chemotherapy. Serum FSH levels of the patients were 5.62 +/- 3.43 mIU/ml before chemotherapy, and 19. 70 +/- 17.06 mIU/ml (p < 0.05) at the time of its completion. Serum FSH levels could reflect damage to spermatogenesis in these cases. Cases in which spermatogenesis did not recover may have higher serum FSH levels than those with recovery of spermatogenesis.

Adolescent↗

[Effects of anti-cancer agents on cultured rat Sertoli cells].

We performed primary immature Sertoli cell culture to investigate whether or not anti-cancer agents would have a direct effect on rat Sertoli cells. Sertoli cells, isolated from testes of 18-day-old rats, were cultured in pellets with medium for 5 days. The concentration of transferrin in cultured medium were measured as the function of Sertoli cells. The anti-cancer agents cis-diamminedichloroplatinum (CDDP), adriamycin and vinblastine were selected for this study, and added to the culture medium. CDDP decreased the level of transferrin concentration in cultured medium, namely 0.5 microgram/ml of CDDP resulted in 54.9% of the transferrin concentration in the medium compared with that without any anti-cancer agents (p < 0.05), and 1.0 micrograms/ml of CDDP produced transferrin concentrations of 57.5% and 46.2% (p < 0.05), respectively. Adriamycin (0.4 microgram/ml) and vinblastine (0.5 microgram/ml) produced transferrin concentrations of 35.2% and 31.3% in cultured medium (p < 0.05), respectively. These findings revealed that anti-cancer agents have direct damaging effects on rat Sertoli cells.

Animals↗

[Studies of spermatogenic damages induced by anti-cancer agent and anti-androgenic agents in rat testes].

To investigate the mechanisms responsible for and recovery process of spermatogenic damage induced by anti-cancer agent and anti-androgen agents, we experimented with rats injected with those agents. Cis-diamminedichloroplatinum (CDDP) was selected as the anti-cancer agent causing spermatogenic damage. Flutamide and cyproterone acetate were selected as anti-androgen agents. Both of these agents induced histopathological spermatogenic damage. The influences of CDDP on spermatogonia and spermatocytes were remarkable, compared with cyproterone acetate and flutamide, which damaged mainly spermatids. CDDP had severely damaging effects on the DNA-synthesizing activity of spermatogenesis, based on findings using monoclonal antibody proliferating cell nuclear antigen (PCNA), compared with anti-androgen agents. We also studied Sertoli cell function of drug-induced spermatogenic damage in rat testes. Measuring the contents of transferrin in rat testes indicated the damage to Sertoli cell function. High doses of CDDP (8 mg/kg) affected testicular transferrin concentration, but 4 mg/kg and 2 mg/kg of CDDP had no significant effect on Sertoli cell function. Cyproterone acetate and flutamide had severely damaging effects on Sertoli cell function not only at a high dose (30 mg/kg) but at low doses of 15 mg/kg and 7.5 mg/kg. These results showed that an anti-cancer agent primarily affects the DNA synthesizing activity of spermatogonia and spermatocytes, but high doses of these agents also have damaging effect on Sertoli cells, and anti-androgen agents mainly affect Sertoli cells.

Androgen Antagonists↗

[Effect of follicle-stimulating hormone (FSH) on protection or acceleration to recovery from spermatogenic damage induced by anti-cancer agents].

We investigated spermatogenic damage induced by anti-cancer agents in previous studies. The results showed that the damage to spermatogenesis induced by anti-cancer agents could be due to not only direct damaging effects on DNA synthesis but also a direct effect on Sertoli cell function. Thus, stimulating Sertoli cell function could protect against the damaging effects of anti-cancer agents on spermatogenesis, or stimulate recovery from impair spermatogenesis. We experimented with rats injected with the anti-cancer agents cisdiamminedichloroplatinum (CDDP) and adriamycin, which impair spermatogenesis, in order to examine this hypothesis. Follicle-stimulating hormone (FSH), which should stimulate Sertoli cell function in vivo, was selected, and the effects of FSH in protecting against damage or stimulating recovery from damage were investigated. The injection of FSH resulted in no significant differences in the histopathological findings of spermatogenic damage induced by anti-cancer agents or testicular transferrin concentration as compared to those observed without FSH injection. But, in the protocol of the experiments on acceleration of recovery from spermatogenic damage induced by anti-cancer agents, the spermatid index without FSH was 1.02 +/- 0.24, that with FHS 75 IU/kg was 1.50 +/- 0.15, and that with FSH 150 IU/kg was 1.62 +/- 0.39, a significant difference (p < 0.05). Also, the PCNA labeling index and testicular transferrin concentration were significantly different with FSH from those without FSH.

Animals↗

Dynamic activities of the frontal association cortex in calculating and thinking.

We found 5-7 Hz magnetic theta waves in the frontal association cortex of adult human subjects during calculation and musical imagination by using 37-channel SQUID gradiometers. Simultaneous recording from the left and right cerebral hemispheres with two sets of 37-channel gradiometers revealed that the theta activity appeared in a waxing and waning manner in the frontal cortices of both hemispheres during the mental exercises. Electrical current dipoles for the theta waves were estimated to occur repeatedly and scatteringly in various parts of the frontal lobes of both hemispheres during continuous and intense mental exercises for 2 min. The results suggest a dynamic mode of activities in the frontal association cortex during mental effort such as calculating and thinking.

Adult↗

Electrophysiology of globus pallidus neurons in vitro.

1. We investigated the electrical properties of globus pallidus neurons intracellularly using brain slices from adult guinea pigs. Three types of neurons were identified according to their intrinsic electrophysiological properties. 2. Type I neurons (59%) were silent at the resting membrane level (-65 +/- 10 mV, mean +/- SD) and generated a burst of spikes, with strong accommodation, to depolarizing current injection. Calcium-dependent low-frequency (1-8 Hz) membrane oscillations were often elicited by membrane depolarization (-53 +/- 8 mV). A low-threshold calcium conductance and an A-current were also identified. The mean input resistance of this neuronal type was 70 +/- 22 M omega. 3. Type II neurons (37%) fired spontaneously at the resting membrane level (-59 +/- 9 mV). Their repetitive firing (< or = 200 Hz) was very sensitive to the amplitude of injected current and showed weak accommodation. Sodium-dependent high-frequency (20-100 Hz) subthreshold membrane oscillations were often elicited by membrane depolarization. This neuronal type demonstrated a low-threshold calcium spike and had the highest input resistance (134 +/- 62 M omega) of the three neuron types. 4. Type III neurons (4%) did not fire spontaneously at the resting membrane level (-73 +/- 5 mV). Their action potentials were characterized by a long duration (2.3 +/- 0.6 ms). Repetitive firing elicited by depolarizing current injection showed weak or no accommodation. This neuronal type had an A-current and showed the lowest input resistance (52 +/- 35 M omega) of the three neuron types. 5. Stimulation of the caudoputamen evoked inhibitory postsynaptic potentials (IPSPs) in Type I and II neurons. In Type II neurons the IPSPs were usually followed by rebound firing. Excitatory postsynaptic potentials and antidromic responses were also elicited in some Type I and II neurons. The estimated conduction velocity of the striopallidal projection was < 1 m/s (Type I neurons, 0.49 +/- 0.37 m/s; Type II neurons, 0.33 +/- 0.13 m/s).

Animals↗

The distribution of the globus pallidus neurons with input from various cortical areas in the monkeys.

Single neuron activities of the globus pallidus were recorded in awake monkeys. Electrical stimulation of various cortical areas (the prefrontal, premotor, supplementary motor and arcuate premotor areas, and the motor cortex) inhibited spontaneous discharge of pallidal neurons. This inhibitory response was considered to be mediated through the striatum. Considerable number of pallidal neurons responded to the stimulation of more than one cortical areas. However, the neurons receiving inputs from the motor cortex and/or arcuate premotor area and those receiving inputs from the prefrontal, premotor and/or supplementary motor areas were segregated. The former neurons were located ventrolaterally in the caudal part of the globus pallidus, while the latter ones were located dorsomedially in the rostral part of the globus pallidus.

Animals↗

No-go activity in the frontal association cortex of human subjects.

'No-go potential', specific to the no-go reaction in go/no-go reaction-time hand movement with discrimination between different colour light stimuli, was recorded with electrodes chronically implanted in the prefrontal cortex of monkeys. Similar potentials were widely distributed over frontal-parietal parts of the human scalp on the same no-go reaction. In this report, MEG measurement was made over the scalp of five healthy subjects in order to localize current sources responsible for the scalp potential. We found in- and outflow of magnetic fields over the dorsolateral frontal parts of the head, contra- and ipsilateral to the operant hand. These magnetic fields were most reasonably interpreted to be due to current dipoles localized in the dorsolateral parts of frontal lobes in both contra- and ipsilateral hemispheres, presumably in the prefrontal-premotor areas. No-go decision and subsequent suppression of voluntary movements are suggested to be one of the functional features of the human frontal association cortex, as in the case of monkeys.

Adult↗

Cerebello- and pallido-thalamic pathways to areas 6 and 4 in the monkey.

Projections from the cerebellar nuclei (CN) and the internal segment of the globus pallidus (GPi) to areas 6 and 4 via the thalamus were examined electrophysiologically in monkeys. In addition to the well-known pallido-thalamo-cortical projection to area 6, some thalamic neurons with CN input were found to project to area 6. Seventeen neurons in VLc, area X and the dorsal margin of VPLo were activated antidromically by stimulation of supplementary motor or premotor areas, and orthodromically by CN stimulation. Twelve neurons in area X and the medial part of VPLo were found to receive CN input and to project to the arcuate premotor area (APA). Four neurons in the VLo-X border region which were identified to project to APA were inhibited by GPi stimulation.

Animals↗

Movement-related activity of thalamic neurons with input from the globus pallidus and projection to the motor cortex in the monkey.

Thalamic neurons projecting to the arm area of the motor cortex were identified by their antidromic response to stimulation of that area in two awake monkeys. Neurons were further identified as receiving inputs from the cerebellar nuclei or the internal segment of the globus pallidus by excitatory or inhibitory response to stimulation of these nuclei. Most (33/34) of the thalamic neurons in the cerebello-thalamo-cortical projection and more than half (12/18) of those in the pallido-thalamo-cortical projection changed their firing rate on the lever-lifting hand movement in the reaction-time task. A considerable number of neurons of both groups (14/23 and 3/10) changed their firing rate prior to the onset of the earliest EMG. These findings agree with the model that activities of pallidal as well as cerebellar nuclear neurons related to motor control are transmitted to the motor cortex through the thalamus.

Animals↗

Discharge patterns of pallidal neurons with input from various cortical areas during movement in the monkey.

Activities of pallidal neurons were studied in awake monkeys which were implanted with stimulating electrodes in the various cortical areas in the frontal lobe. Cortical inputs to each pallidal neuron were examined by inhibitory responses to stimulation through these electrodes. Discharge patterns of pallidal neurons were observed during performance of the reaction-time, delayed go/no-go discrimination and self-paced movement tasks. Most of the pallidal neurons with input from the arm of the motor cortex changed their firing rate in close relation to the arm movement (movement-related activity). Many of the neurons with input from the supplementary motor and cingulate areas showed sustained changes in discharge rate during the delay period in addition to movement-related activity. Most of the neurons with input from prefrontal cortex responded to light stimulus.

Animals↗

Projection on the motor cortex of thalamic neurons with pallidal input in the monkey.

The cortical projection areas of thalamic neurons with basal ganglia and/or cerebellar inputs were studied electrophysiologically in unanesthetized monkeys. Thalamic neurons which receive inhibition from the pallidum were found to project to the motor cortex (area 4) as well as to premotor cortex. The neurons with pallidal input and motor cortical projection were located mainly in VLo. This result indicates that the basal ganglia innervate the motor cortex through the thalamus. Thus the basal ganglia can modify the cortical output for controlling movements directly through this pathway as compared with its influence through the prefrontal and premotor cortices.

Action Potentials↗