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Biomedical subjects

A Mikami

Publications and source records attributed to A Mikami.

At least 19 recordsLinked to original sources

From three-dimensional space vision to prehensile hand movements: the lateral intraparietal area links the area V3A and the anterior intraparietal area in macaques.

The posterior parietal cortex is included in the dorsal cortical visual pathway underlying the three-dimensional (3-D) visual recognition of space and objects. The neurons in the lateral intraparietal area (LIP) respond visually to the three-dimensional objects, whereas those in the anterior intraparietal area (AIP) respond to hand movements to grasp them. LIP receives visual inputs from V3A, whereas AIP projects to the premotor areas; however, it is not known whether the neurons in LIP project to AIP. We herein investigated the connectional substrates that underlie the transformation of three-dimensional vision to prehensile hand movements in the Japanese monkey (Macaca fuscata). After identifying the three-dimensional visually responsive region in the posterior part of LIP by the unit recordings, we injected a bidirectional tracer, wheat germ agglutinin conjugated to horseradish peroxidase, into one of the recording sites. We found that LIP receives neuronal projections from V3A and sends axons to AIP. To confirm our findings, we injected several orthograde tracers into V3A and retrograde tracers into AIP in the same hemispheres. We found that the V3A neurons projecting to LIP terminate in the vicinity of the LIP neurons projecting to AIP. The results suggest that the cortical connections of V3A-LIP-AIP in the lateral bank of the intraparietal sulcus play an important role in the visuomotor transformation for prehensile hand movements.

Animals↗

Electroretinogram analysis of relative spectral sensitivity in genetically identified dichromatic macaques.

The retinas of macaque monkeys usually contain three types of photopigment, providing them with trichromatic color vision homologous to that of humans. However, we recently used molecular genetic analysis to identify several macaques with a dichromatic genotype. The affected X chromosome of these animals contains a hybrid gene of long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) photopigments instead of separate genes encoding L and M photopigments. The product of the hybrid gene exhibits a spectral sensitivity close to that of M photopigment; consequently, male monkeys carrying the hybrid gene are genetic protanopes, effectively lacking L photopigment. In the present study, we assessed retinal expression of L photopigment in monkeys carrying the hybrid gene. The relative sensitivities to middle-wavelength (green) and long-wavelength (red) light were measured by electroretinogram flicker photometry. We found the sensitivity to red light to be extremely low in protanopic male monkeys compared with monkeys with the normal genotype. In female heterozygotes, sensitivity to red light was intermediate between the genetic protanopes and normal monkeys. Decreased sensitivity to long wavelengths was thus consistent with genetic loss of L photopigment.

Animals↗

Anterior cingulate activity during pain-avoidance and reward tasks in monkeys.

We recorded single neuronal activities in the anterior cingulate cortex of monkeys while they were performing discriminative pain-avoidance and reward tasks: a prediction cue was presented for 0.5-1.5 s, followed by a red or green discrimination cue (1:1, random) for 1.0 s; painful stimuli were presented if the monkey failed to respond during the red cue; a reward was given, subsequent to a cued 1 s delay, if the monkey responded after the green cue. Among 775 neurons recorded, 196 neurons showed significant activity during one or more observation periods; 36 during the prediction period; 77 during the discrimination period; 41 during the delay period; 85 during the response period; 40 during the pre-reward period; and 15 during the reward-ingestion period. Of 77 neurons activated during the discrimination period, 47 showed exclusive activity either during the red (34) or during the green (13) cue: of 85 neurons activated during the response period, 64 showed exclusive activity either for pain-avoidance (37) or obtaining a reward (27). Control experiments confirmed that the neuronal activity could not be attributed to simple visual or motor processes. The results suggest that some anterior cingulate neurons are involved with anticipation of, and response selection for, imminent events.

Action Potentials↗

Association of gastroesophageal reflux disease with weight gain and apnea, and their disturbance on sleep.

Obesity is a common predisposition to gastroesophageal reflux disease (GERD) and obstructive sleep apnea syndrome (OSAS). By statistical analysis of the respondents to a questionnaire that was distributed to members of the Kansai Rugby Association, we examined whether weight gain increased the incidence of these diseases and whether GERD alone disturbs sleep. Prevalence distribution of GERD by age differed from another survey, which suggests that predispositions other than age may contribute to GERD. Weight gain tended to increase the incidence of GERD. In our epidemiological study, both GERD (particularly nocturnal reflux) and OSAS significantly contributed to sleep disturbance. Although GERD alone seemed to be one of several independent factors of sleep disturbance, it was not a weak factor.

Adult↗

New compound heterozygous mutation in the CYP17 gene in a 46,XY girl with 17 alpha-hydroxylase/17,20-lyase deficiency.

BACKGROUND: 17alpha-Hydroxylase/17,20-lyase deficiency is caused by a defect of P450c17 which catalyzes both 17alpha-hydroxylase and 17,20-lyase reactions in adrenal glands and gonads. RESULTS: In the present study, we analyzed the CYP17 gene in a Japanese patient with 17alpha-hydroxylase/17,20-lyase deficiency. The patient was a phenotypic girl and referred to us for right-sided inguinal hernia at the age of 4 years. Biopsy of the herniated gonad showed testicular tissue. The karyotype was 46,XY. At 6 years of age, hypertension was clearly recognized and the patient was diagnosed as having 17alpha-hydroxylase/17,20-lyase deficiency based on the clinical and laboratory findings. Analysis of the CYP17 gene revealed a compound heterozygous mutation. One mutation was an undescribed single nucleotide deletion at codon 247 in exon 4 (CTT to CT: 247delT) and the other was a missense mutation resulting in a substitution of His to Leu at codon 373 in exon 6 (CAC to CTC: H373L), which has been previously shown to abolish both 17alpha-hydroxylase and 17,20-lyase activities. The functional expression study of the 247delT mutant showed that this 247delT mutation completely eliminates both 17alpha-hydroxylase and 17,20-lyase activities. CONCLUSIONS: Together, these results indicate that the patient is a compound heterozygote for the mutation of the CYP17 gene (247delT and H373L) and that these mutations inactivate both 17alpha-hydroxylase and 17,20-lyase activities and give rise to clinically manifest 17alpha-hydroxylase/17,20-lyase deficiency.

Adrenal Hyperplasia, Congenital↗

[A case of congenital esophagobronchial fistula discovered incidentally on esophagography].

A 50-year-old man was admitted to our hospital because of an abnormal shadow, detected during an upper gastrointestinal examination. A chest radiograph showed an infiltrating shadow in the right middle lung field. A chest CT showed a fistula communicating between a bronchus (rt. B6) and the middle of the esophagus. Resection of the fistula was performed by video-assisted thoracoscopic surgery (VATS). Isolation of the fistula was straightforward, and there was no evidence of inflammation or adherent lymph nodes around it. Histologic examination of the resected specimen revealed that the fistula lumen was covered with squamous epithelium and muscularis mucosa. These findings suggested that this case could be categorized as Braimbridge type II. In this case, the chest CT showed the esophagobronchial fistula clearly, and was useful for the diagnosis.

Bronchial Fistula↗

During pain-avoidance neurons activated in the macaque anterior cingulate and caudate.

Lesions in either the anterior cingulate cortex (ACC) or the caudate nucleus (CN) impair avoidance behavior from noxious somatic stimuli, so these two areas may play a similar role in pain-avoidance behavior. To test this hypothesis, we recorded single neuronal activities in the ACC and in the CN of a monkey while it was performing a pain-avoidance task. Ten of 136 ACC and eleven of 160 CN neurons responded selectively during pain-avoidance behavior. We found little difference in the population distribution or in the response latency and duration. Our present findings are in accordance with previous lesion and anatomical studies which suggest that these two regions could function as one module in pain-avoidance behavior.

Animals↗

An axonemal dynein at the Hybrid Sterility 6 locus: implications for t haplotype-specific male sterility and the evolution of species barriers.

Poor sperm motility characterized by a distinct aberration in flagellar waveform known as "curlicue" is a hallmark of t haplotype (t) homozygous male sterility. Previous studies have localized "curlicue" and a flagellar developmental defect, "whipless", to the Hybrid Sterility 6 locus (Hst6), between the markers Pim1 and Crya1. More recent heterospecific breeding experiments between Mus spretus (Spretus) and Mus musculus domesticus (Domesticus) have mapped the primary source(s) of both "curlicue" and "whipless" to a small sub-locus of Hst6, Curlicue a (Ccua). Here we report the complete physical isolation of the Ccua locus and the identification of a candidate gene for expression of both "whipless" and "curlicue" at its proximal end, an axonemal dynein heavy chain gene, Dnahc8, formerly mapped by interspecific backcross analysis near Pim1. Dnahc8 mRNA expression commences in the Domesticus wild-type testis just prior to flagellar assembly and is testis-specific in the adult male. However, expression of Dnahc8 is not readily evident in the testis of either Spretus or "whipless" animals (Domesticus males homozygous for the Spretus allele of Dnahc8). Our results argue that Dnahc8 is fundamental to flagellar organization and function in Domesticus, but not Spretus, and suggest that Dnahc8 is integral to both Hst6- and t-specific male infertility.

Animals↗

Treatment for pyothorax-associated lymphoma.

In eight patients with pyothorax-associated lymphoma (PAL), which resulted from artificial pneumothorax for the treatment of pulmonary tuberculosis, seven patients received radiotherapy and five showed no local recurrence. All four patients treated by primary chemotherapy had disease progression. Radiotherapy of 50 Gy with wide margins is recommended to treat PAL.

Aged↗

Esophageal pressure and apnea hypopnea index in sleep-disordered breathing.

Severity of negative esophageal pressure (Pes) and apnea hypopnea index (AHI) were investigated in six cases of upper airway resistance syndrome (UARS) and 11 cases of obstructive sleep apnea syndrome (OSAS). The severity of negative Pes was represented by the highest peak (Pes Max) and the number of increased episodes (more than 13.5 cmH2O) per h (NPesI13.5). There was no significant correlation between Pes indices and AHI. Pes Max and NPesI13.5 were not different among severe OSAS (AHI > 30), mild OSAS (AHI < 30) and UARS. Apnea hypopnea index failed to represent the severity of negative Pes, which is an important aspect of the pathophysiology of sleep-disordered breathing.

Adult↗

Erythropoietin receptors that signal through Stat5 or Stat3 support fetal liver and adult erythropoiesis: lack of specificity of stat signals during red blood cell development.

Erythropoietin (Epo) is essential for formation of mature red blood cells (RBC). However, the function of Epo receptor (EpoR)-dependent signaling pathways in the regulation of erythropoiesis remains unclear. To determine whether specific Stat signals are required for RBC development, we changed the Stat signaling specificity of the EpoR. The wild-type EpoR activates only Stat5. Thus, we substituted the major Stat5 binding sites (residues 343 and 401) in the EpoR cytoplasmic region with the Stat3 binding/activation motif from gp130. We demonstrated that activated EpoRs containing a single substitution stimulate Stat5 and Stat3, whereas an EpoR with both substitutions stimulates Stat3 but not Stat5. We then determined the ability of these receptors to support fetal liver and adult erythropoiesis. Our results show that erythropoiesis is stimulated by EpoRs that activate Stat5, both Stat5 and Stat3, or Stat3 in place of Stat5. These findings demonstrate that the specificity of EpoR Stat signaling is not essential for RBC development.

Animals↗

Search target selection in monkey prefrontal cortex.

To explore a visual scene, the brain must detect an object of interest and direct the eyes to it. To investigate the brain's mechanism of saccade target selection, we trained monkeys to perform a visual search task with a response delay and recorded neuronal activity in the prefrontal (PF) cortex. Even though the monkey was not allowed to express its choice until after a delay, the response field of a class of PF neurons was able to differentiate between target and distractors from the very beginning of their response (135 ms). Strong responses were obtained only when the target was presented at the field. Neurons responded much less during a nonsearch task in which saccade target was presented alone in this response field. These results suggest that the PF cortex may be involved in the decision-making process and the focal attention for saccade target selection.

Animals↗

Developmental changes in enzyme activities and in morphology of rat cortex mitochondria.

Development of mitochondria in rat brain cortex was investigated in terms of mitochondrial respiratory enzyme activities, and structural and numerical developments of mitochondria. Measurements of succinate-O2 and NADH-O2 oxidoreductase activities of mitochondria resulted in simultaneous changes of activities in postnatal rat. Both oxidoreductase activities were still low at 0-5 days old, increased until 15 days, decreased slightly at 21 days and drastically in adult mitochondria. In morphological study, the cross-sectional area of mitochondrion per cell increased gradually until 21 days old, but decreased drastically in adult. The area of a mitochondrion at 5 days increased about 1.5-fold in comparison with that at 0 days, and maintained at 15 and 21 days. However, the values of area of one mitochondrion from 10 days and adult are about half of a maximum value (21 days). Numbers of mitochondrion per cell were still low at 0-5 days, and high constantly (about twice) at 10-21 days. These findings suggest that the organelle division of mitochondria may be carried out at 5-10 days postnatal. The number of adult rat mitochondria decreased slightly. The small and undeveloped mitochondria were observed at 0 day postnatal by use of transmission electron microscopy (TEM). However, during development from 5 days postnatal, larger and elongated mitochondria were observed, and the maximal complexity of structure of cristae is observed at 15 days and 21 days by TEM. In adult cortex, the small mitochondria were also observed with compact and dense cristae. Our results indicate that the changes of activities of mitochondrial respiratory enzymes in rat cortex is good correlated with the structural maturation of mitochondria.

Animals↗

Behavior of blood cells in contact with water-soluble phospholipid polymer.

Omega-Methacryloyloxyalkyl phosphorylcholine (MAPC) polymer, which has various methylene chain lengths between the phosphorylcholine group and the backbone, was synthesized with attention to formation of the biomembrane. The effect of water-soluble poly(MAPC) on the function and activation of blood cells was evaluated to determine the interaction between blood cells and the MAPC polymer. The poly(MAPC) and the MAPC copolymer with a small amount of fluorescent units were synthesized by a conventional radical polymerization technique. Using a fluorescence spectrometer, it was determined that the MAPC polymer was adsorbed on the plasma membrane of platelets when the platelets were suspended in an aqueous solution of the MAPC copolymer. The hemolytic activity of poly(MAPC) was less than that of other water-soluble polymers, such as poly(ethylene glycol) and poly(1-vinyl-2-pyrrolidone) (PVPy). The change in the plasma membrane fluidity of platelets on contact with poly(MAPC) was determined with 1,6-diphenyl-1,3,5,-hexatriene. The plasma membrane fluidity of platelets decreased with an increase in the methylene chain length of the MAPC unit. The aggregation activity of platelets after contact with poly(MAPC) was also evaluated, but no significant difference between that of polymer-contacted platelets and native platelets was observed. Finally, the activity of platelets on contact with poly(MAPC) was determined by measuring the cytoplasmic calcium ion concentration ([Ca2+]i) in platelets. The increase in [Ca2+]i in the platelets after contact with poly(MAPC) was similar to that of native platelets. We conclude that the poly(MAPC) reduced platelet activation even though the poly(MAPC) adsorbed on the membrane surface of the platelets. In particular, poly(10-methacryloyloxydecyl phosphorylcholine) significantly reduced platelet activation compared with PVPy.

Adsorption↗

Oligomerization and scaffolding functions of the erythropoietin receptor cytoplasmic tail.

Signal transduction by the erythropoietin receptor (EPOR) is activated by ligand-mediated receptor homodimerization. However, the relationship between extracellular and intracellular domain oligomerization remains poorly understood. To assess the requirements for dimerization of receptor cytoplasmic sequences for signaling, we overexpressed mutant EPORs in combination with wild-type (WT) EPOR to drive formation of heterodimeric (i.e. WT-mutant) receptor complexes. Dimerization of the membrane-proximal portion of the EPOR cytoplasmic region was found to be critical for the initiation of mitogenic signaling. However, dimerization of the entire EPOR cytoplasmic region was not required. To examine this process more closely, we generated chimeras between the intracellular and transmembrane portions of the EPOR and the extracellular domains of the interleukin-2 receptor beta and gammac chains. These chimeras allowed us to assess more precisely the signaling role of each receptor chain because only heterodimers of WT and mutant receptor chimeras form in the presence of interleukin-2. Coexpression studies demonstrated that a functional receptor complex requires the membrane-proximal region of each receptor subunit in the oligomer to permit activation of JAK2 but only one membrane-distal tail to activate STAT5 and to support cell proliferation. Thus, this study defines key relationships involved in the assembly and activation of the EPOR signal transduction complex which may be applicable to other homodimeric cytokine receptors.

Base Sequence↗