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Biomedical subjects

A Mikami

Publications and source records attributed to A Mikami.

At least 55 records · Page 3Linked to original sources
PubMed1997

Neuronal activity in the frontal eye field of the monkey is modulated while attention is focused on to a stimulus in the peripheral visual field, irrespective of eye movement.

We tested the hypothesis that the frontal eye field (FEF) is involved in attention to the peripheral visual field (PVF). Neuronal activity was recorded in the FEF of two monkeys while they were performing three oculomotor tasks. In the visual attention task (VAT), the monkeys released a lever when a test stimulus (TS) presented in the PVF dimmed while they were looking at a central fixation point (FP). In the visual saccade task (VST), the monkeys exhibited saccadic eye movements when the FP was extinguished. In the visual fixation task (VFT), the monkeys released the lever when the FP dimmed. Overall, the activities of 80 FEF neurons were examined. The responses to visual stimuli of 41 of these neurons (51%) were modulated during the VAT. Twenty-five neurons showed pre-saccadic activity. Of these, 13 neurons (52%) exhibited activity modulation during the VAT. Eighteen neurons showed no pre-saccadic activity. Of these, 10 neurons (56%) exhibited activity modulation during the VAT. These results suggest that the FEF is involved in selecting the visual stimuli relevant to performing a task irrespective of eye movements.

Animals↗
PubMed1997

Visual receptive fields and movement fields of visuomovement neurons in the monkey premotor cortex obtained during a visually guided reaching task.

Single-neuron activity in the premotor cortex of monkeys was examined while they performed a visually guided reaching task with their eyes fixated. We recorded a total of 177 visually responsive neurons that showed significantly enhanced activity after a presentation of visuospatial cue ('visual response'). Of these neurons, 57% (n = 101) also showed significantly enhanced activity after an onset of the go-signal and before movement ('movement-associated response'). These were designated as 'visuomovement neurons'. The visual response latencies of 81% of the visuomovement neurons were between 60 and 160 ms (median = 100 ms) and the response durations were less than 240 ms in 80% of the neurons. The preferred direction of the visual response (PDV) was toward the contralateral side in 57% and the ipsilateral side in 20% of the neurons. The preferred direction of the movement-associated response (PDM) was toward the contralateral side in 50% of the neurons. In most of the neurons (74/101, 73%), the PDV and the PDM corresponded to approximately the same direction. These results suggest that premotor visuomovement neurons play a role in receiving visuospatial information for visually guided reaching, and commanding reaching movements.

Animals↗
PubMed1997

Conventional molecular diagnosis of steroid 21-hydroxylase deficiency using mismatched primers and polymerase chain reaction.

We tested a conventional method based on polymerase chain reaction (PCR) and specific primers with one mismatched base at the 3' end to introduce restriction enzyme sites in order to detect mutations of the CYP21 gene without radioisotope. Using this method, the intron 2 mutation causing aberrant splicing of mRNA (In2G) and the exon 4 mutation (Ile->Asn, Ex4) in the CYP21 gene were analyzed. The nonsense mutation in exon 8 (Ex8NON) of the CYP21 gene was also investigated by PCR and subsequent restriction enzyme digestion. The mismatched primers successfully amplified the CYP21 gene containing the In2G and the Ex4 mutation sites, and the presence of these two mutations could be determined by restriction enzyme digestion after PCR. We used this new method to study 33 patients. Twenty-five of these patients were found to have at least one mutation (In2G and/or Ex4 mutation). By enzyme digestion after PCR, the Ex8NON mutation was also identified (7 out of 33 patients). In conclusion, we have developed a new method to detect point mutations in the CYP21 gene. This method was proved to be sensitive and rapid for the detection of the mutations studied. Therefore, this method is suitable for clinical genetic diagnosis.

Adrenal Hyperplasia, Congenital↗
PubMed1996

Multiple mouse chromosomal loci for dynein-based motility.

Dyneins are multisubunit mechanochemical enzymes capable of interacting with microtubules to generate force. Axonemal dyneins produce the motive force for ciliary and flagellar beating by inducing sliding between adjacent microtubules within the axoneme. Cytoplasmic dyneins translocate membranous organelles and chromosomes toward the minus ends of cytoplasmic microtubules. Dynactin is an accessory complex implicated in tethering cytoplasmic dynein to membranous organelles and mitotic kinetochores. In the studies described here, we have identified a number of new dynein genes and determined their mouse chromosomal locations by interspecific backcross analysis. We have also mapped several dynein and dynactin genes cloned previously. Our studies provide the first comprehensive attempt to map dynein and dynactin genes in mammals and provide a basis for the further analysis of dynein function in development and disease.

Amino Acid Sequence↗
PubMed1996

In vitro motility from recombinant dynein heavy chain.

The dyneins are a class of motor protein involved in ciliary and flagellar motility, organelle transport, and chromosome segregation. Because of their large size and subunit complexity, relatively little is known about their mechanisms of force production and regulation. We report here on the expression and analysis of the entire rat cytoplasmic dynein heavy chain (Mr 532,000). Full-length cDNAs were constructed from a series of partial clones and tagged at the C terminus with either a FLAG-epitope tag or a His6-tag. The recombinant polypeptides were expressed either in insect cells by baculovirus infection or in COS-7 cells by transient transfection. The recombinant protein was mostly soluble and showed good microtubule binding. It exhibited a broad sedimentation profile, indicative of the formation of dimers as well as higher order multimers. Good microtubule gliding motility activity was observed in assays of heavy chain expressed in either insect or COS-7 cells. Average microtubule gliding velocities of 1.2-1.8 microm/sec were observed, comparable with the rates determined for calf brain cytoplasmic dynein. These results represent the first indication that recombinant heavy chain alone is capable of force production, and should lead to rapid progress in defining the dynein motor domain.

Amino Acid Sequence↗
PubMed1996

A new isopatulin derivative pintulin produced by Penicillium vulpinum F-4148 taxonomy, isolation, physico-chemical properties, structure and biological properties.

During our screening program of natural products from fungal metabolites for drugs effective against tumor cell lines, we discovered a new isopatulin derivative, pintulin, from the fermentation broth of Penicillium vulpinum F-4148. Pintulin shows weak activity against tumor cell lines, compared to that of adriamycin.

Antibiotics, Antineoplastic↗
PubMed1995

Visual neurons with higher selectivity can retain memory in the monkey temporal cortex.

Activities of individual neurons were recorded from the superior temporal sulcus (STS) of rhesus monkeys during the performance of a visual discrimination and memory task. Of 174 neurons analyzed in detail, 19 neurons showed sustained changes in discharge rates during the delay period (D neurons). All the D neurons showed responses during the presentation of the same stimulus and had higher selectivity compared to the remaining non-D neurons. The data indicated that a subgroup of highly selective visual neurons in the STS participate in short-term retention of these stimuli.

Animals↗
PubMed1995

Local injection of bicuculline into area 8 and area 6 of the rhesus monkey induces deficits in performance of a visual discrimination GO/NO-GO task.

While performing a symmetrically reinforced visual discrimination GO/NO-GO task, five monkeys were injected with a GABAA antagonist, bicuculline methiodide (BMI), into Brodmann's area 9, 8, 6, or 4. The task consisted of five periods: START, OFF, CUE, RESPONSE, and an inter-trial interval. The monkey was trained to make either the GO response (lever release) or the NO-GO response (continued pressing of the lever), depending on the color of the cue, during the RESPONSE period. Analysis was limited to 102 sites in which muscle convulsions of the forelimb and/or shoulder did not result from BMI injections. Errors in performance increased 10-60 min after injection into 10 of 33 sites in area 9, 9 of 25 sites in area 8, 20 of 34 sites in area 6, and 2 of 10 sites in area 4. The number of trials finished in a 120-min session decrease. Injections induced PRE-RESPONSE errors (release of the lever in either the OFF or CUE periods), GO RESPONSE errors (failure to release the lever when signaled), and NO-GO RESPONSE errors (release of the lever despite a signal not to release). The results suggest that both areas 8 and 6 are involved in correct performance of the GO/NO-GO task.

Animals↗
PubMed1995

Effect of transcranial magnetic stimulation on cerebral function in a monkey model.

The effect of transcranial magnetic stimulation on higher cerebral function was studied using 3 monkeys. They were trained in a delayed response task which required spatial short-term memory. The task was presented by a computer on a cathode-ray tube and results of the delayed response task, which consisted of the percentage of correct choices, reaction time and trial number, were analyzed. For stimulation, small and large round coils were used as well as a figure 8 configuration. Their maximal B-fields were 3.3 T, 1.9 T and 2.4 T, respectively. A total of more than 7000 stimuli were given to each monkey in various patterns. There was no deficit in the delayed response. Further complications such as epileptic seizures were not observed either. In conclusion, transcranial magnetic stimulation does not appear to have any effect on higher cerebral functions in monkeys.

Animals↗
PubMed1994

Neuronal responses to photographs in the superior temporal sulcus of the rhesus monkey.

The activity of a total of 174 visual neurons in the superior temporal sulcus (mostly area TE) of rhesus monkeys was examined quantitatively using complex visual stimuli. Colored photographs of human faces (n = 411), monkeys (n = 308), and non-face objects (n = 35), as well as computer-generated graphics were presented as visual stimuli during a performance of a visual discrimination task. All neurons responded to a limited number of photographs. We quantified these stimulus-selective responses, using two kinds of selectivity indices. With the first index (SI1), we attempted to estimate how many stimuli produced a significant response. The mean value of SI1 was 0.63. About 31% of neurons had values of SI1 greater than 0.8. With the second index (SI2), we attempted to estimate how many stimuli could be distinguished from the stimulus that elicited the strongest activity. The mean value of the SI2 was 0.71. About 51% of neurons had values of SI2 greater than 0.8. About 66% of neurons had values of either SI1 or SI2 that were greater than 0.8, a value that corresponds to a selectivity of one out of five stimuli. We designated these neurons as stimulus-selective (SS) neurons. Of these SS neurons, 45% showed the best response to human faces. Similarly, 28.8% showed the best response to a photograph of monkeys. 7.5% to food, 8.8% to non-food and 10% to simple graphics, such as, a colored square or a circle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Visual response properties of single neurons in the temporal pole of behaving monkeys.

1. The responses of single neurons in the anterior part of the temporal cortex in monkeys, mainly the temporopolar cortex, area 36, and the most anterior part of area TE of von Bonin and Bailey (1947) (these areas were designated here as the temporal pole), were examined during the performance of a visual recognition memory task. The visual stimulus (sample stimulus) was presented when the monkey pressed a lever. The same sample stimulus was presented one to four times and, thereafter, a new stimulus was presented. The monkeys were trained to discriminate the new stimulus from the sample stimulus and to release the lever in response to the new stimulus. We used colored photographs of natural objects (human faces, monkeys, foods, and non-food objects) as complex visual stimuli or computer-generated two-dimensional shapes (a red square, a green circle, etc.) as simple visual stimuli. 2. In total, the activity of 311 neurons was recorded, and 225 of these responded to at least one visual stimulus. All visually responsive neurons were located in the ventral part of the temporal pole including the banks of the superior temporal sulcus. 3. The relationship between the monkey's eye movements and visual responses was investigated. Visual response properties, such as the number of spikes, onset latency, and response duration, were stable regardless of the monkey's eye positions and movements if the eyes were directed to the display. We also examined the receptive field property of neurons (n = 3). The neurons tested in the temporal pole tended to have a large receptive field (24 x 24 degrees). 4. The neurons tended to respond to different stimuli in different magnitudes. In each case, the maximal responses were elicited by complex, colored photographs, whereas simple, two-dimensional colored shapes elicited little or no responses. In 21% of the cases (47/225), the magnitude of the maximal response was significantly larger than for any of the other responses. 5. An achromatic version of the stimulus that induced the maximal response was tested in 53 neurons. About 80% of the neurons (41/53) responded to the achromatic stimulus at a magnitude that was not significantly different from the response to the original stimulus. In 12 neurons, the removal of color did significantly decrease the magnitude of the response. When other colors were tested, 3 of 9 neurons were found to code for color. 6. In 21 of these 53 neurons, a portion (the left-, right-, upper-, or lower-half) of the stimulus was also tested.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Molecular cloning of the retrograde transport motor cytoplasmic dynein (MAP 1C).

Overlapping cDNAs encoding the entire heavy chain of cytoplasmic dynein (MAP 1C) have been obtained. A 4644 amino acid polypeptide containing four ATP-binding consensus sequences is predicted. Homology with the sea urchin flagellar outer arm dynein beta heavy chain is observed within the C-terminal two-thirds of the protein. The N-terminal third of the two polypeptides shows no clear relationship, suggesting that this region of MAP 1C is responsible for its association with retrograde organelles and other functions. Northern blot analysis reveals a 16.5 kb band in brain and other tissues. Southern blot analysis is consistent with a single cytoplasmic dynein gene. Thus, in contrast with cilia and flagella, which contain numerous forms of dynein, our results are consistent with the existence of only a single cytoplasmic dynein heavy chain gene, which appears to produce only a single transcript.

Amino Acid Sequence↗
PubMed1992

Development of the ability to detect visual motion in infant macaque monkeys.

A preferential looking technique was used to measure detection of visual motion by 12 infant macaque monkeys (10 Macaca fuscata and 2 Macaca mulatta at ages between 1 and 100 days). A 0.25 cycles/deg square-wave grating was presented at speeds from 40 to 0.4 deg/s. The threshold was determined by a two-alternative forced-choice preferential looking method, in conjunction with a staircase procedure. The threshold for detection of visual motion decreased exponentially with age over the first 100 days of life. At each age there was substantial variability among the individual infants tested, but each monkey's ability to detect visual motion improved with age.

Aging↗
PubMed1992

Spatiotemporal characteristics of direction-selective neurons in the middle temporal visual area of the macaque monkeys.

In an attempt to elucidate the mechanisms of directional selectivity in the neurons of the middle temporal visual area (MT) of macaque monkeys, we presented small numbers of sequentially flashed stimuli with various temporal and spatial intervals within the receptive field (RF) of direction-selective MT neurons. Experiments were performed using awake macaque monkeys trained to fixate on a set of short stationary lines. Stimuli were presented on a CRT screen under computer control. In two-flash experiments, responses to a test flash presented in the center of the RF were examined following a conditioning flash presented in various locations within the RF. Inhibition in the null direction was observed in about 78% of MT neurons, while facilitation was relatively weak in this group of neurons. In most of these neurons, the ranges of temporal and spatial intervals that produced directional selectivity in two-flash experiments were within half the values and double the values, respectively of those in multi-flash experiments. In the remaining 22% of direction-selective MT neurons, several flashed stimuli were necessary to produce directional selectivity. Most of these neurons showed facilitation in the preferred direction. It appears that the inhibitory mechanisms in the null direction are sufficiently strong to be induced by a single conditioning flash whereas the facilitatory mechanisms are weaker and several stimuli are required for production of the direction-selective response.

Animals↗
PubMed1992

Homology of the 74-kD cytoplasmic dynein subunit with a flagellar dynein polypeptide suggests an intracellular targeting function.

In previous work we found cytoplasmic dynein to be a complex of two catalytic heavy chains and at least seven co-purifying polypeptides of unknown function. The most prominent of these is a 74-kD electrophoretic species which can be resolved as two to three bands by SDS-PAGE. We have now selected a series of overlapping rat brain cDNAs encoding the 74-kD species. The deduced sequence of a full-length cDNA predicts a 72,753 D polypeptide which includes the amino acid sequences of nine peptides determined by NH2-terminal microsequencing. PCR performed on first strand rat brain cDNA together with the sequence of a partially matching tryptic peptide indicated the existence of at least three isoforms of the 74-kD cytoplasmic dynein subunit. Comparison with known sequences revealed that the carboxyl-terminal half of the polypeptide is 26.4% identical and 47.7% similar to the product of the Chlamydomonas ODA6 gene, a 70-kD intermediate chain of flagellar outer arm dynein. Immunoblot analysis with a monoclonal antibody to the 74-kD species indicated a widespread tissue distribution, as expected for a cytoplasmic dynein subunit. Nonetheless, the antibody recognized a 67-kD species in ram sperm flagella and pig tracheal cilia, supporting the existence of distinct but related cytoplasmic and axonemal polypeptides in mammals. In view of evidence for a role for the ODA6 gene product in anchoring flagellar dynein to the A subfiber microtubule in the axoneme, we predict an analogous role for the 74-kD polypeptide, perhaps in mediating the interaction of cytoplasmic dynein with membranous organelles and kinetochores.

Amino Acid Sequence↗
PubMed1992

Oscillatory neuronal activity related to visual short-term memory in monkey temporal pole.

The activity of single neurons was recorded extracellularly from the temporal pole of monkeys while they were performing a visual short-term memory task. Neurons in the ventral part of the temporal pole showed sustained firing during the memorization delay period of the task when the monkey was remembering particular visual stimuli. The presence and absence of the firing were correlated with the correct and incorrect performance of the task, respectively. The sustained firing showed oscillation. The data suggest that visual information was stored as sustained firing among certain group of neurons producing oscillations.

Animals↗
PubMed1992

Activity of single neurons in the monkey amygdala during performance of a visual discrimination task.

1. The activity of single neurons was recorded extracellularly from the monkey amygdala while monkeys performed a visual discrimination task. The monkeys were trained to remember a visual stimulus during a delay period (0.5-3.0 s), to discriminate a new visual stimulus from the stimulus, and to release a lever when the new stimulus was presented. Colored photographs (human faces, monkeys, foods, and nonfood objects) or computer-generated two-dimensional shapes (a yellow triangle, a red circle, etc.) were used as visual stimuli. 2. The activity of 160 task-related neurons was studied. Of these, 144 (90%) responded to visual stimuli, 13 (8%) showed firing during the delay period, and 9 (6%) responded to the reward. 3. Task-related neurons were categorized according to the way in which various stimuli activated the neurons. First, to evaluate the proportion of all tested stimuli that elicited changes in activity of a neuron, selectivity index 1 (SI1) was employed. Second, to evaluate the ability of a neuron to discriminate a stimulus from another stimulus, SI2 was employed. On the basis of the calculated values of SI1 and SI2, neurons were classified as selective and nonselective. Most visual neurons were categorized as selective (131/144), and a few were characterized as nonselective (13/144). Neurons active during the delay period were also categorized as selective visual and delay neurons (6/13) and as nonselective delay neurons (7/13). 4. Responses of selective visual neurons had various temporal and stimulus-selective properties. Latencies ranged widely from 60 to 300 ms. Response durations also ranged widely from 20 to 870 ms. When the natures of the various effective stimuli were studied for each neuron, one-fourth of the responses of these neurons were considered to reflect some categorical aspect of the stimuli, such as human, monkey, food, or nonfood object. Furthermore, the responses of some neurons apparently reflected a certain behavioral significance of the stimuli that was separate from the task, such as the face of a particular person, smiling human faces, etc. 5. Nonselective visual neurons responded to a visual stimulus, regardless of its nature. They also responded in the absence of a visual stimulus when the monkey anticipated the appearance of the next stimulus. 6. Selective visual and delay neurons fired in response to particular stimuli and throughout the subsequent delay periods. Nonselective delay neurons increased their discharge rates gradually during the delay period, and the discharge rate decreased after the next stimulus was presented. 7. Task-related neurons were identified in six histologically distinct nuclei of the amygdala.(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗