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Biomedical subjects

R Hashimoto

Publications and source records attributed to R Hashimoto.

At least 73 records · Page 4Linked to original sources

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↗

Melanoxazal, new melanin biosynthesis inhibitor discovered by using the larval haemolymph of the silkworm, Bombyx mori. Production, isolation, structural elucidation, and biological properties.

A new melanin biosynthesis inhibitor, melanoxazal, was isolated from the fermentation broth of Trichoderma sp. ATF-451 by successive purification procedures of carbon adsorption, ethyl acetate extraction and silica gel column chromatography. The inhibitor possesses a novel oxazole-containing structure with molecular formula, C8H9NO3. The structure was determined by means of NMR analyses to be (E)-4-(2'-formyl-3'-hydroxybuten-1'-yl) oxazole, which is related to melanoxadin. Melanoxazal inhibited melanin formation in the larval haemolymph of the silkworm, Bombyx mori; IC50 value = 30.1 micrograms/ml. Melanoxazal also showed a strong inhibitory activity against mushroom tyrosinase with IC50 value = 4.2 micrograms/ml.

Animals↗

[Preserved implicit reading and the recovery of explicit reading in a pure alexic].

We described a 55-year-old, right-handed, university-educated Japanese man who showed pure alexia after an infarction in the territory of the left posterior cerebral artery. Damage to the corpus callosum was limited to the most caudal part of the splenium. In the early days of his illness, he demonstrated the inability to read aloud on either Kana (Japanese syllabograms) or Kanji (Japanese morphograms). In contrast, he could semantically categorize Kanji-words such as animals or non-animals. Subsequently, he gradually regained the ability of reading aloud Kanji as well as Kana. At that time, we further investigated the relation between his reading ability and the attributes of 881 Kanji characters including hieroglyphicity, concreteness, and familiarity. We found that he could more readily read Kanjis with higher hieroglyphicity, concreteness, and familiarity. The reading times for Kanji-words were significantly shorter than those of corresponding Kana-words. Moreover, he showed some difficulty to read Kana-words and Kana combinations without meaning when asked to perform repetitive opposing movements with his thumb and little finger inhibiting kinesthetic reading. The effect was not observed when he read Kanji-words. These results lead us to suggest the following: (1) the two components of reading, reading aloud and comprehension abilities, are dissociable in a pure alexic, especially in Kanji reading; and (2) recovery mechanisms underlying Kanji and Kana reading were different in our case. Namely, restitution of the direct connection through the residual splenium fibers between the visual word form processing area in the right hemisphere and the left angular gyrus was attributed to Kanji reading, and utilization of kinesthetic reading played an important role in Kana reading.

Dyslexia, Acquired↗

Hyperinsulinaemia as a predictor of hypertension: an 11-year follow-up study in Japan.

OBJECTIVE: To examine the hypothesis that hyperinsulinaemia is associated with the development of borderline hypertension or hypertension. DESIGN: Blood pressure status in non-obese normotensives (< 140/90 mmHg, n = 135) people were re-examined after 11 years after the baseline examination. Participants were selected from a 1981 population-based health examination and had a high blood glucose level or more than a trace of glucose in their urine. Out of 319 people recruited for further examination of glucose tolerance status, 135 normotensive participants with body mass index < 26 kg/m2 and without diabetes according to World Health Organization criteria were re-examined at the follow-up survey. RESULTS: Sixty-two (46%) out of 135 normotensive participants were hypertensive (defined as blood pressure > or = 140/90 mmHg) or receiving antihypertensive medication (n = 8) at the follow-up survey. Significant associations between the development of hypertension and baseline parameters were observed for systolic and diastolic blood pressure, serum triglycerides, high-density lipoprotein (HDL)-cholesterol, fasting and 60 min post-load insulin levels, and the sum of insulin concentrations from fasting to 180 min after glucose challenge after adjustments for age and sex. Odds ratios (95% confidence intervals) for the future development of hypertension between the highest and the lowest tertiles of insulin levels were 4.06 (1.40-11.76) for fasting insulin, 4.25 (1.45-12.45) for 60 min post-glucose load insulin, and 3.88 (1.34-11.20) for the sum of insulin concentrations, after adjustment for age, sex, systolic blood pressure, body mass index and alcohol consumption. Further adjustments for serum triglycerides and serum creatinine did not affect the insulin-hypertension relationship. CONCLUSION: The present study suggests that hyperinsulinemia is significantly related to the development of hypertension in non-obese and non-diabetic Japanese people.

Adult↗

[A case of rapidly grown pulmonary blastoma].

A 78-year-old woman who had been in a local hospital with a complaint of cough and chest pain was referred to our hospital because a mass 12 cm in size was found in her right lung by a chest X-ray and CT. Within 3 weeks, the tumor rapidly developed to 19 cm in size. Malignant schwannoma of the lung was suspected by a percutaneus lung biopsy and the right upper and middle lobectomy was performed. Histological analysis of the tumor showed a biphasic structure with epithelial and mesenchymal component which was diagnosed pulmonary blastoma. Pulmonary blastoma is very rare, but it may be of benefit for the thoracic surgeon to establish methods of diagnosis and treatment of this disease.

Aged↗

[Truncal valvoplasty for post-operative truncal valve regurgitation of truncus arteriosus: a case report].

The surgical treatment for truncal valve regurgitation is still controversial in patients with truncus arteriosus. A two-year-old girl with complaints of low weight gain and tachypnea was referred for treatment of truncal valve regurgitation. She had undergone an emergency pulmonary artery banding for severe congestive heart failure due to truncus arteriosus-type I at six months of age. This anomaly had been corrected by Barbero-Marcial method at seven months of age. But the truncal valve regurgitation started appearing at sixteen months of age with the progression of the stenosis of the pulmonary artery orifice and the right ventricular outflow tract regurgitation. Echo cardiography and cineangiography revealed the truncal valve to be bicuspid, and the regurgitation severe, especially through the prolapsed left sided cusp. The truncal valve was repaired by commissural suspension method, and the right ventricular outflow tract reconstructed with patch angioplasty of the pulmonary artery orifice and Carpentier-Edwards pericardial Bioprosthesis (19 mm). The post-operative course was uneventful. One year after, truncal valve regurgitation is small by color Doppler study. We conclude that valvoplasty is to be considered as the first choice of treatment for truncal valve regurgitation.

Child, Preschool↗

N-terminal deletion mutants of insulin-like growth factor-II (IGF-II) show Thr7 and Leu8 important for binding to insulin and IGF-I receptors and Leu8 critical for all IGF-II functions.

To define the role of the N-terminal region of insulin-like growth factor-II (IGF-II) in its binding to insulin and IGF receptors, deletion mutants des-(1-5)-, des-(1-7)-, and des-(1-8)-recombinant (r) IGF-II, and the Gly8 for Leu substitution mutant of rIGF-II were prepared by site-directed mutagenesis, expressed in Escherichia coli, and purified. The binding affinity and mitogenic activity of these rIGF-II mutants as well as commercially available des-(1-6)-rIGF-II were analyzed. While the relative affinity of des-(1-5)- and des-(1-6)-rIGF-II for purified human insulin and IGF-I receptors remained at > or = 50% levels of that of rIGF-II, the affinity of des-(1-7)-rIGF-II decreased to approximately 10% and approximately 3%, respectively, of that of rIGF-II. When the octapeptide including Leu8 was removed prior to the Cys9-Cys47 intrachain bond, the relative affinity of this deletion mutant, des-(1-8)-rIGF-II, for these receptors dramatically decreased to < 1% of that of rIGF-II. Substituting Gly8 for Leu in rIGF-II decreased the affinity of this mutant for the IGF-I and insulin receptors to about the same extent. These results suggest that the side chains of Thr7 and Leu8 may play an important role in retaining all of the IGF-II functions. Decreases in the relative affinity for binding of the mutants to these receptors paralleled the decreases in their mitogenic potency for cultured Balb/c 3T3 cells. Although the relative affinity of des-(1-8)- or [Gly8]rIGF-II for rat IGF-II/CIM6-P (cation-independent mannose 6-phosphate) receptors was also < 1% of that of rIGF-II, the relative affinities of des-(1-5)-, des-(1-6)-, and des-(1-7)-rIGF-II for these receptors was significantly greater than that of rIGF-II. These results clearly demonstrate that Thr7 and Leu8 are important for binding to insulin and IGF-I receptors and Leu8 is critical for expression of all IGF-II functions.

3T3 Cells↗

Purified horseshoe crab factor G. Reconstitution and characterization of the (1-->3)-beta-D-glucan-sensitive serine protease cascade.

Horseshoe crab hemocyte lysate responds to (1-->3)-beta-D-glucans, initiating an enzymatic cascade, which culuminates in clot formation. We have purified to homogeneity the serine protease zymogen factor G, which is directly activated by (1-->3)-beta-D-glucans and which initiates the hemolymph clotting cascade. Factor G is a heterodimeric protein composed of two noncovalently associated subunits alpha (72 kDa) and beta (37 kDa). In the presence of (1-->3)-beta-D-glucans such as curdlan and paramylon, factor G is autocatalytically activated to an active serine protease named factor G. This activation is accompanied by limited proteolysis of both subunits: the 72-kDa subunit alpha is cleaved to 55-kDa and 17-kDa fragments, and the 37-kDa subunit beta is shortened to 34 kDa. Longer incubations with (1-->3)-beta-D-glucans result in cleavage of the 55-kDa fragment to 46 kDa and the 34-kDa fragment to 32 kDa, with concomitant loss of amidase activity. Reconstitution experiments using purified proteins participating in the hemolymph clotting cascade demonstrate that factor G is capable of activating proclotting enzyme directly, resulting in the conversion of coagulogen to coagulin gel. Thus, purified factor G is shown to be the primary initiator of the (1-->3)-beta-D-glucan-sensitive coagulation pathway in the horseshoe crab hemocyte lysate.

Amino Acid Sequence↗