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Biomedical subjects

R Hashimoto

Publications and source records attributed to R Hashimoto.

At least 19 recordsLinked to original sources

Pulse exposure of cultured rat neurons to aluminum-maltol affected the axonal transport system.

Although chronic aluminum neurotoxicity has been well established, the mechanism of the toxicity has not been elucidated yet. In order to simplify the study of the aluminum neurotoxicity, we employed the pulse exposure of cultured rat cortical neurons to 250 microM aluminum-maltol for 1 h at the early stage (6 h after plating), which resulted in abnormal distribution of neurofilament L (NFL) and fast axonal transported proteins, whereas the axonal transport of tubulin, actin, and clathrin were not impaired. Otherwise, the pulse exposure of neurons at the late stage (4 days after plating) to the same concentration of aluminum-maltol did not affect the cell morphology and the distribution of NFL. The pulse exposure of cultured neurons to aluminum-maltol at the early stage might affect the axonal transport system of NFL and fast axonal transported proteins.

Actins

Selective kana jargonagraphia following right hemispheric infarction.

A strongly right-handed Japanese man showed an unusual writing disorder associated with Broca-type aphasia after suffering a right hemispheric infarction. Writing with his right hand produced a fluent output in contrast to his nonfluent speech. The patient's agraphia disproportionately affected the writing of kana (Japanese syllabograms), leaving relatively intact the writing of kanji (Japanese ideograms). His kana agraphia, consisting of substitutions, intrusions, transpositions, and deletions, became apparent as the number of syllables in target words increased. Quantitative analysis of the substitutions in terms of their phonological similarity to the target revealed that most of the substitutions were phonologically dissimilar. Those errors were distributed almost identically for familiar and novel words. Moreover, the errors were observed asymmetrically across the target: more errors occurred near the end than at the beginning of a word. The kana agraphia in association with fluent writing output resulted in kana jargonagraphia. These observations suggest that our patient's selective kana jargonagraphia is best explained by selective damage to the hypothesized kana graphemic buffer and by disinhibition of the motor engrams of writing behavior, both of which resulted from right hemispheric damage.

Agraphia

Domain- and site-specific phosphorylation of bovine NF-L by Rho-associated kinase.

Rho-associated kinase (Rho-kinase), the putative target of the small GTP-binding protein Rho, phosphorylated neurofilament protein (NF-L) in vitro with approximately 1 mole phosphate per mole NF-L. Phosphorylated NF-L no longer formed the 10 nm filaments, and NF-L filaments were phosphorylated with a result of nearly complete disassembly. NF-L phosphorylated by Rho-kinase was digested with trypsin, and digested fragments were assigned by MALDI/TOF. Unique phosphorylation sites were found at Ser-26 and Ser-57 in the head domain of NF-L. These results indicate that domain- and site-specific phosphorylation by Rho-kinase may regulate the assembly-disassembly of NF-L filaments.

Amino Acid Sequence

Clustering of cardiovascular risk factors in hyperinsulinemia in Japanese without diabetes.

Clustering of cardiovascular risk factors in hyperinsulinemia was investigated in 247 Japanese subjects without diabetes. After adjustment for age and sex, the highest quartile of the summed values of insulin concentrations after oral glucose loading showed high odds ratios (OR; 95% confidence intervals) for the prevalence of cardiovascular risk factors: OR = 2.02 (1.07-3.83) for hypertension, 3.91 (1.82-8.40) for hypertriglyceridemia, 2.41 (1.30-4.46) for low high-density lipoprotein cholesterol, 2.41 (1.28-4.51) for impaired glucose tolerance, and 3.58 (1.44-8.88) for high uric acid. Two or more of these factors were clinically elevated in 50% of those in the highest quartile of the summed values of insulin, compared to 16-28% of those in the lower three quartiles. These findings were slightly attenuated after further adjustment for body mass index and sum of skinfolds. In conclusion, multiple risk factors for cardiovascular disease existed in the subjects with hyperinsulinemia in Japanese without diabetes.

Adult

Contribution of the supplementary motor area and anterior cingulate gyrus to pathological grasping phenomena.

To investigate the relationship between the site of brain damage and characteristics of the pathological grasping phenomena, we examined different varieties of the reaction in a consecutive series of 28 patients with unilateral hemispheric damage due to stroke. Patients with a lesion relatively confined to the supplementary motor area (n = 4) constantly exhibited a grasp reflex, mainly in the hand contralateral to the lesion, but they never showed a groping reaction. By contrast, patients with damage primarily involving the anterior cingulate gyrus (n = 3) developed the groping reaction in the hand contralateral to the lesion, but they had only a very mild grasp reflex in that hand. Patients with damage involving both the supplementary motor area and the anterior cingulate gyrus (n = 12) showed the grasp reflex and groping reaction mainly in the hand contralateral to the lesion. Patients with damage to the medial parietal lobe (n = 2), those with damage to the lateral convexity of the hemisphere (n = 6), and a patient with damage confined to the corpus callosum did not exhibit such grasping phenomena. From these observations, we conclude that the grasp reflex is closely related to a lesion of the supplementary motor area, whereas the groping reaction is bound to a lesion of the anterior cingulate gyrus.

Adult

Induction of ectopic corticotropic tumor in mouse embryos by exo utero cell transplantation and its effects on the fetal adrenal gland.

To establish an in vivo experimental system for developmental endocrinology research, AtT-20 cells, a corticotropic tumor cell line, were transplanted by exo utero manipulation into mouse embryos on embryonic day 14. The induced tumor secreted ACTH in situ, and the circulating ACTH level was elevated. This was the first model for studying the regulation of ACTH in the mouse fetal adrenal in vivo and the first continuous ACTH treatment model in rodent fetuses. The changes in the adrenal gland from the tumor-induced embryos were analyzed by light microscopic morphometry, immunohistochemistry for steroidogenic enzymes, and electron microscopy. In the treated adrenal, the volume of the inner cortical zone was significantly larger than that in controls. In the inner zone, cell density was decreased, and average cell size was increased, whereas bromodeoxyuridine-incorporation was not increased. The enlarged inner zone cells expressed an enhanced level of cytochrome P45011beta, the corticosterone-synthesizing enzyme, and the serum corticosterone level was increased. Electron microscopy showed an active form of the organelles involved in steroidogenesis. These findings indicate that ACTH stimulates both adrenocortical hypertrophy and steroidogenesis in fetal mice. Potential perspectives of the novel paradigm in this research for molecular developmental endocrine study are discussed.

Adrenal Glands

[Compulsive manipulation of tools in the left hand following damage to the right medial frontal lobe].

In 1982, Mori and Yamadori first reported a woman who showed compulsive manipulation of tools (CMT) following an infarction in the left medial frontal lobe. When an object was shown, the patient's right hand reached, grasped and manipulated it properly against her will. Since then, there have been many similar case reports and CMT has been generally believed to occur in the right hand after damage to the left medial frontal lobe. However, there also have been a few case reports of CMT in the left hand of a patient with damage to the right medial frontal lobe. To clarify whether such a patient with CMT in the left hand is an exceptional case or not, we prospectively investigated CMT in the left hand of 10 patients with an infarction in the right medial hemisphere. All patients were examined within 6 weeks after stroke. Magnetic resonance images were used to determine the location and extension of a lesion. We found that 7 cases with a lesion involving the anterior cingulate gyrus (ACG) and the supplementary motor area (SMA) exhibited a grasp reflex and a visual grouping mainly in the left hand. Five of these 7 cases had a lesion extending into the middle and anterior parts of the ACG and displayed CMT in the left hand. Among those 5 patients, 2 with a lesion which was extensive enough into the ACG to involve almost entirely the anterior part of it adjoining the genu and anterior body of the corpus callosum showed a prominent CMT in the left hand. Two patients with a lesion principally confined to the SMA showed the grasp reflex and some subvarieties of the instinctive grasp reaction mainly in the left hand, but never showed visual grouping nor CMT. One patient with a lesion involving the posterior cingulate gyrus and medial parietal lobe but sparing both the SMA and ACG showed neither grasping responses nor CMT. From these observations, we conclude the following: (1) it is not an exceptional case that a right-handed patient with a right medial frontal lesion shows CMT in the left hand: and (2) extensive damage to the ACG involving its anterior part adjoining the genu and anterior body of the corpus callosum is most crucial for the development of CMT.

Adult

Binding sites and binding properties of binary and ternary complexes of insulin-like growth factor-II (IGF-II), IGF-binding protein-3, and acid-labile subunit.

We have examined regions of rat IGF-binding protein-3 (IGFBP-3) important for complex formations using two kinds of deletion mutants, three kinds of chimera molecules between rat IGFBP-3 and rat IGFBP-2, and a synthetic peptide (41 residues, Glu52-Ala92) derived from rat IGFBP-3. Solid-phase binding assays using 96-well microtiter plates were designed to quantitate the relative binding affinities. It was found that not only the IGFBP-3 derivatives with the amino-terminal, cysteine-rich domain (N domain) but also the synthetic peptide maintained affinity for IGF-II. Ternary complex formation was observed with full-length IGFBP-3 and chimera IGFBP, the carboxyl-terminal cysteine-rich domain (C domain) of which was derived from IGFBP-3, unlike the mutants lacking the C domain and the chimera IGFBPs, the C domain of which was derived from IGFBP-2. These results were confirmed by affinity cross-linking experiments. Furthermore, the IGFBP-3 derivatives that possessed the C domain of IGFBP-3 bound to the acid-labile subunit, even in the absence of IGFs. Finally, we observed sites in IGF-II important for the ternary complex formation using various IGF-II mutants. These IGF-II mutants, which contained a substitution of Tyr27 for Leu, had extremely reduced activity. These results strongly suggest that: 1) the N domain, containing at least Glu52-Ala92, of rat IGFBP-3 is important for binding to IGF-II; 2) the C domain of IGFBP-3 is essential for binding to the acid-labile subunit both in the presence and absence of IGF-II; and 3) Tyr27 of IGF-II is important for the ternary complex formation.

Animals

Selective translocation of different markers in the ante- and retrograde pathways between the Golgi apparatus and the rough endoplasmic reticulum in a hybridoma cell line.

We examined the effects of brefeldin A (BFA, 10 micrograms/ml), an inhibitor of protein transport, on the redistribution of different markers of the Golgi apparatus (GA) in hybridoma H35 cells to examine selective transport of marker molecules between the rough endoplasmic reticulum (RER) and the GA. In H35 cells, the GAs had several cisternae with cis and trans faces as deduced by morphology such as relationship with RER and secretory granules. Thiamin pyrophosphatase (TPPase) was distributed in the trans elements, mannosidase II (man II) was in the cis-medial elements, and deposits of Zinc-Iodide-Osmium (ZIO) staining were localized in the cis/intermediate compartment. Upon BFA treatment for 5 min, man II and TPPase were redistributed in all cisternae. After 10 min of BFA treatment, TPPase activity was observed only in the RER, while the cis/intermediate compartment as evidenced by ZIO staining and man II remained. Upon clearance of BFA from the medium, cisternal structures with man II and ZIO staining reappeared at 30 min. TPPase activity was detected in the GA only after 120 min. Thus, in the retrograde pathway, the trans marker, TPPase moves earlier than the cismedial markers, man II and ZIO staining, whereas in the antegrade pathway, the cis-medial markers move earlier than the trans marker. These results suggest that BFA first alters the characteristic enzyme localization before the GA vanishes into the RER, and that selective transport mechanisms may exist for components of different stacks of the GA.

Animals

Hyperinsulinemia and the development of ST-T electrocardiographic abnormalities. An 11-year follow-up study.

OBJECTIVE: It has been suggested that insulin resistance and consequent hyperinsulinemia promote atherosclerosis, but few prospective studies have reported the relationships between hyperinsulinemia and the development of ST-T abnormalities in the 12-lead resting electrocardiogram (ECG) in populations in which atherosclerosis is rare. RESEARCH DESIGN AND METHODS: A total of 304 Japanese men and women, aged 20-69 years, selected for having high blood glucose or more than a trace-positive urine glucose from a population-based health examination in 1981, were followed for 11 years. Of these, 33 died, 1 from myocardial infarction, while 260/271 living were reexamined in 1992. The 237 subjects with a normal ECG at the baseline examination were analyzed. RESULTS: Incident ST-T abnormalities occurred in 13/237 people. Insulin concentrations were positively associated with the development of ST-T abnormalities (relative risk approximately 8, comparing those in the highest versus lowest quartile of insulin values). Adjustment for age, sex, and systolic blood pressure or other risk factors had little effect on this relationship. CONCLUSIONS: Hyperinsulinemia was related to the development of ST-T abnormalities in ECGs in the absence of the development of clinical signs of atherosclerosis, independent of blood pressure and other risk factors in men and women with mild glucose intolerance.

Adult

Degenerative hairlets on the vestibular sensory cells in mutant bustling (BUS/Idr) mice.

The bustling mouse (BUS/Idr: bus) is a mutant mouse strain which exhibits deafness, bustling/hyperkinetic behaviour and functional disorders seemingly related to the vestibular system. This phenotype develops in homozygous (bus/bus) mice and has been shown from cross experiments to be genetically induced by a single autosomal recessive gene. We previously detected, with light and electron microscopy, post-natal degeneration of the inner ear sensory cells in homozygotes. In the present study, we examined, by electron microscopy, the development of pathological changes in the sensory epithelia of the macula acustica and crista ampullaris of homozygous mice of various ages, paying special attention to the detailed morphology of the sensory hairlets. The homozygous mice exhibited specific pathological changes: a decrease in the number of hairs; disarrangement of the kinocilium-stereocilia pattern; and, fused and/or very large stereocilia. Homozygotes also frequently exhibited apical cytoplasmic herniation, or bleb of hair cells, as well as a degenerated kinocilium in the sensory epithelium. Heterozygotes showed similar changes, but to a lesser degree and frequency. As for the vestibular organs, similar pathological changes had developed at day, 17 of gestation. These pathological findings and onset suggest that the BUS mouse may be a mutant mouse strain distinct from other reported strains which display similar behaviour, and may be a useful animal model for the study of human degenerative vestibular disorders.

Animals

[Left hand clumsiness due to disturbance of kinesthesia after damage to the dorsal column of the high cervical cord].

We described a 48-year-old, right-handed woman who manifested left hand clumsiness after damage to the dorsal column of the high cervical cord due to probable multiple sclerosis. On February 29, 1996, she developed a weakness in the right limbs. Subsequently, she suffered numbness and clumsiness in the left limbs, even though muscle strength of the left limbs was preserved. Seventeen days later, she was referred to our hospital. A T2-weighted MRI after admission demonstrated high signal intensities in the left dorsal column and the right antero-lateral part of the cervical cord at the C1 to C3 vertebral level. Under the diagnosis of probable multiple sclerosis, steroid pulse therapy was applied twice and she gradually regained muscle strength in the right limbs and sensation in the left limbs. One month later, elemental sensations such as pain, touch, temperature, vibration, and position, as well as discriminative sensations such as localization sensation, two-point discrimination, barognosis, pinch-press discrimination, and graphesthesia in the left limbs returned to normal. However, her left hand remained clumsy, especially when she tried to manipulate objects. She also showed a great difficulty in sustaining a constant level of pinching force by the left thumb and index finger, and in localizing her right thumb placed in space with the left hand with her eyes closed. She stated herself that she could not sense at all how her left hand and fingers were moving. Somatosensory evoked potentials recorded from the right scalp showed that the NI was poorly organized and the patency of subsequent peaks was delayed. Transcranial magnetic stimulation revealed that the pyramidal tract from the right motor cortex to the left cervical cord was functionally intact. These observations lead us to conclude as follows: (1) the patient's left hand clumsiness is probably due to the disturbance of kinesthesia, which is crucial to activate temporo-spatial patterns of complex hand and finger movements as well as to maintain long sequences of simple motor execution without vision; and (2) kinesthesia is a specific sensation that is presumably conveyed by the dorsal columns and could be selectively affected by a cervical cord lesion.

Female

Diagonistic dyspraxia. Clinical characteristics, responsible lesion and possible underlying mechanism.

We present three patients who showed, in addition to signs of callosal interruption, a variety of abnormal motor behaviour of the left hand dissociated from conscious volition, in the absence of pathological grasping phenomena. The abnormal movements of the left hand consisted of (i) antagonistic movements to the right; (ii) non-antagonistic, irrelevant movements to the right; (iii) symmetric movements to the right in which the left hand sometimes preceded the right, and (iv) occasional inability to move at will during a bimanual task. From these observations and a review of previous publications, we propose that, in most right-handed subjects; diagonistic dyspraxia could be defined as abnormal motor behaviour of the left hand activated by voluntary movements of the right hand. Motor phenomena similar to diagonistic dyspraxia but attributable to impulsive groping movements induced by medial frontal lobe pathology should be excluded from diagonistic dyspraxia. Comparison of MRIs of the three patients with those of five patients who developed no diagonistic dyspraxia following an infarction of the corpus callosum, with or without medial hemispheric involvement, revealed that damage to the ventral part of the posterior end of the body of the corpus callosum was crucial for the development of diagonistic dyspraxia. Since the commissural fibres between the superior parietal lobules pass through the caudal part of the body of the corpus callosum, and also since there is accumulating evidence that the human superior parietal lobule is concerned with selection of movement based on the integration of visual and/or somatosensory information, we infer that diagonistic dyspraxia is produced by a disconnection of the right superior parietal lobule from the left which is dominant for volitional control of movement in most right-handed subjects.

Apraxias

Gigantic aneurysm in the thoraco-abdominal aorta of an infant.

We report the case of a boy with a gigantic aneurysm in the thoraco-abdominal region which was detected by a chest X-ray taken prior to surgical correction of ptosis of the eyelids at 11 months of age. At 18 months, he successfully underwent aneurysm exclusion and bypass grafting. A biopsy from the thoracic aorta revealed medial degeneration with conspicuous smooth muscle cell involvement. Laboratory examination showed altered elastase activity in the granulocytes and whole blood. The present case may represent a unique form of aneurysm in infancy.

Aortic Aneurysm, Abdominal

Thoracoabdominal aortic aneurysm in an infant treated by thromboexclusion with thoracoabdominal aortic bypass. A case report.

A case of a huge thoracoabdominal aortic aneurysm in an eighteen-month-old boy is reported. Surgical treatment was successfully performed by thromboexclusion of the aneurysm with thoracoabdominal aortic bypass using a low-porosity woven Dacron graft 10 mm in diameter and of sufficient surplus length. During the early postoperative period, he developed moderate hydronephrosis, owing to compression of the left ureter by the graft, but no further deterioration was seen. Follow-up angiographies performed four and six years after surgery revealed straightening of the graft and slight stretching of the aorta at the distal anastomosis, but no stenosis was found. Now, seven and a half years after surgery, he has no pressure gradient between upper and lower extremities.

Angiography, Digital Subtraction