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Biomedical subjects

K Miyoshi

Publications and source records attributed to K Miyoshi.

At least 109 records · Page 6Linked to original sources
PubMed1995

Cytoskeletal changes in rat cortical neurons induced by long-term intraventricular infusion of leupeptin.

Neurofibrillary tangles (NFTs), which are composed of paired helical filament (PHF)-like filaments, were induced by the long-term intraventricular infusion of leupeptin, a potent protease inhibitor. The fibrils composing the NFTs were 20 nm in maximal width and had periodic constrictions at 40-nm intervals. They were identical to the PHF that had been found in aged rat neurons. Dystrophic axons filled with mainly tubular structures were also abundantly found in the parietal and temporal isocortices, which were not affected in the acute or subacute phases of leupeptin treatment. An immunohistochemical study using antibodies related to the neuronal cytoskeleton showed that neuronal cytoskeletal changes accompanying ubiquitination occurred in dystrophic axons distributed widely in the isocortex as well as the hippocampal formation. The present findings suggest that long-term administration of leupeptin accelerates the neuronal ageing process in rats and causes other neuronal changes: NFT formation, such as seen in the aged brain or in neurodegenerative diseases including Alzheimer's disease, in addition to accumulation of lipofuscin granules and degeneration of neuronal processes. In other words, some disturbance of the balance between proteases and their inhibitors may play an important role in the neuronal ageing process, and some regulatory intervention in the intraneuronal protease activity may provide a new therapeutic strategy for the neurodegenerative diseases.

Alzheimer Disease↗
PubMed1995

Coexistence of Pick bodies and atypical Lewy bodies in the locus ceruleus neurons of Pick's disease.

We observed abundant Pick argentophilic inclusion bodies (PBs) as well as some atypical Lewy bodies (LBs) in the locus ceruleus (LC) from a patient with Pick's disease. In addition, there were a few neurons which contained both PBs and LBs. PBs in the LC frequently appeared multiple and had lobulated or irregular shapes, though their ultrastructural elements were the same as those of the PBs appearing in the cerebral cortex, and consisted of randomly arranged smooth-surfaced straight tubules of 15 nm in diameter, mixed with a small number of long-period constricted fibrils. The ultrastructure of the LB coexisting with PB was identical with that previously reported; a dense core was surrounded by concentric layers of radially oriented 10-nm filaments and was clearly distinguishable from the PB. Immunohistochemical examination with various antibodies related to neurofibrillar pathology demonstrated that anti-tau antibodies reacted positively with both PB and the rim portion of LB in the present case; an unusual finding for LB. The anti-neurofilament 200-kDa protein stained only LBs, even when PBs and LBs coexisted in the same neuron. These findings show that two kinds of neuronal fibrillar inclusions, whose underlying cytoskeletal abnormalities are thought to be different, can coexist in the same neuron. In addition, the formation of multiple, lobulated PBs may suggest some particularity of cytoskeletal composition of the LC neurons.

Aged↗
PubMed1995

Effects of osmolarity and amino acids in a chemically defined medium on development of rat one-cell embryos.

Rat one-cell embryos, recovered from naturally mated females, were cultured in a chemically defined medium (R1ECM) under different experimental conditions. When the osmolarity of the medium with a reduced concentration (63.8 mmol l-1) of NaCl was varied by adding different amounts of D-sorbitol, more (79-91%) of the one-cell embryos developed to the four-cell stage at 212-278 mosmol than at 306 mosmol (13%). The greatest proportions of morulae (74%) and blastocysts (60%) were obtained at 246 mosmol. When the medium was supplemented with amino acids in various combinations and the osmolarity adjusted to about 246 mosmol, more (80-98%) of the embryos developed to the morula stage. More blastocysts were obtained in medium supplemented with glutamine (Gln: 80%), minimal essential medium (MEM) essential amino acids (EAA) (90%), Gln+EAA (83%), EAA+MEM nonessential amino acids (NEAA) (83%) or EAA+Gln+NEAA (90%) than in medium without amino acids (59%). Few (3-10%) hatching or hatched blastocysts were observed 120 h after the start of culture in the medium with EAA plus Gln or NEAA. The mean number of cells in blastocysts developed in the medium with EAA+Gln+NEAA was 46.7 +/- 7.2. When a total of 82 morulae or early blastocysts that had developed in culture were transferred to eight pseudopregnant rats on day 4, six recipients into which 62 embryos were transferred maintained their pregnancies beyond day 23, although no deliveries had occurred by day 25 or 26. When the rats were killed, 42 (68%) implantation sites and eight (13%) full-term fetuses with no gross abnormality were observed in the uterine horns.

Amino Acids↗
PubMed1995

[Epidemiological study of the prognosis and relevant factors of demented patients].

One hundred twenty patients diagnosed as having dementia at the Center for Elderly Dementia in Hyogo College of Medicine, were recruited for this study to investigate the factors related to the prognosis of dementia. Patients were classified into the following two groups: those staying at home (group 1); those who died at home (group 2). The proportion of various dementias was almost equal in each group: vascular dementia, 30%; senile dementia of Alzheimer's type, 40%; mixed dementia, 20%; Alzheimer's disease, 10%. The average duration of disease in the two groups were not significantly different. The average age of onset in group 2 was higher than that in group 1. The rate of those with severe dementia was higher in group 2 than group 1. Those in group 2 scored less on the Mini-Mental State examination than those in group 1. Symptoms of dementia were assessed by the modified GBS-scale. In group 2, patients scored higher in impaired intellectual and motor functions. The CT findings suggested cortical atrophy, ventricular enlargement and periventricular lucency more often in group 2 than in group 1. Laboratory findings revealed that decrease in red blood cell count, hemoglobin, hematocrit and serum protein were more apparent in group 2 than group 1. It was considered that impaired motor functions, cortical atrophy, white matter lesions, anemia and malnutrition enhanced the probability of death. The study has confirmed that the prognosis of dementia is not only related to intellectual impairment but also deteriorated physical conditions such as motor dysfunction, anemia and malnutrition.

Aged↗
PubMed1995

[Influences of tooth contact patterns during mandibular retrusion on the terminal jaw relation of habitual closures].

Influence of tooth contact patterns during mandibular retrusion on the terminal jaw relation (TJR) of habitual closures were investigated on five subjects. A maxillary stabilization splint with steep retrusive contacts was fabricated and applied to each subject for one week in the first series of this experiment. In the second series, steepness of the retrusive contacts was reduced and the splint with flat occlusal surface was applied. After each series, subjects were asked to perform habitual closures with an intraoral central bearing device and their TJR was recorded. The results as follows: 1. TJR was influenced by the tooth contact pattern during mandibular retrusion. 2. TJR recorded after the second series tended to be more posterior than that after the first series. 3. It was suggested that the position of the condyle might change posteriorly with flatter retrusive contacts. 4. These results suggest the necessity of appropriate tooth guidance during mandibular retrusive movements for the dentulous subjects.

Adult↗
PubMed1995

[A clinical and experimental study of dorsiflexed intercalated segmental instability in a scaphoid fracture].

The purpose of this study was to clarify the pathomechanics of dorsiflexed intercalated segmental instability (DISI) in a scaphoid fracture. Twenty two patients with a scaphoid fracture were used for the clinical study. DISI was recognized in 6 patients. There was no statistically significant difference between the DISI(+) group and the DISI(-) group in total ROM, or in grip strength. In the DISI(+) group, however, ROM shifted dorsally (p < 0.05). Clinical factors for DISI were as follows. (1) pseudoarthrosis without treatment: 2 cases; (2) bone union taking place in a humpbacked position: 3 cases; (3) resection of proximal fragment: 1 case. Two fresh cadavers were used for the experimental study. In one cadaver which received simple osteotomy of the scaphoid, DISI was not seen after 216,000 repeated wrist movements (15 times/min., 10 days). In the other cadaver which underwent a volar wedge osteotomy of the scaphoid, the proximal fragment of the scaphoid and the lunate dorsiflexed temporarily under axial compression force immediately after surgery. After 8 days (172,800 repeated movements), static DISI could be seen without axial compression force. These results suggested that a volar bone defect was important for DISI after a scaphoid fracture. When an axial compression force was added, both the proximal fragment of the scaphoid and the lunate could be dorsiflexed in proportion to the volar bone defect due to the linkage between the proximal fragment and the lunate. Loosening in the surrounding tissue occurred gradually during continuous wrist movement and static DISI was finally observed. Therefore, immediate and proper treatment should be recommended to prevent mal-union as well as non-union.

Adolescent↗
PubMed1994

Impairment in the acquisition of passive and active avoidance learning tasks due to bilateral entorhinal cortex lesions.

The relationship between the entorhinal cortex and learning behavior was examined. The initial stage of Alzheimer's disease has been shown to be characterized by neuropathological alteration in the entorhinal cortex, with the appearance of the greatest number of neuronal tangles and severe neuronal loss in comparison with other brain regions involved. This entorhinal cortex, because of its anatomical relationship to the hippocampus, may play a crucial role in memory formation. In this study, rats with bilateral ibotenic acid-induced lesions of the entorhinal cortices were tested for acquisition of passive and active avoidance learning tasks. These animals displayed no sensorimotor disturbances as shown by evaluation of locomotor activity and shock sensitivity. However, they did show impair acquisition of passive and active avoidance responses. On the other hand, when the lesions were induced after training, there was no extinction of the acquired passive and active avoidance responses. The results demonstrate the importance of the entorhinal cortex in learning acquisition and indicate that rats with partial neuronal loss in the entorhinal cortex may be a useful model for studying the memory disturbance of Alzheimer's disease.

Animals↗
PubMed1994

Effects of AETT-induced neuronal ceroid lipofuscinosis on learning ability in rats.

The behavioral effects of ceroid-lipofuscin accumulation, induced by intraperitoneal administration of acetyl-ethyl-tetramethyl-tetralin (AETT) in Wistar rats for 3 months, were examined in the present studies. A significant increase in neuronal ceroidlipofuscin was demonstrated neuropathologically as well as morphometrically. Although the AETT-intoxicated rats showed neither alteration of locomotor activity nor shock sensitivity, a significant impairment of learning ability, especially an acquisition trial in passive avoidance tests, was observed. Results of the present studies indicate the possibility that a diffuse lipofuscin accumulation causes a learning impairment in rats. The results also imply the possibility of a significant role of age-related lipofuscin accumulation in the dementing processes of human especially in the elderly.

Animals↗
PubMed1994

Identification of causative chemicals of allergic contact dermatitis using a combination of patch testing in patients and chemical analysis. Application to cases from rubber footwear.

5 cases of allergic contact dermatitis from rubber footwear were investigated by a combination of patch testing in patients and chemical analysis of causative rubber products. Our studies revealed 2-mercaptobenzothiazole (MBT) and benzothiazyl disulfide (MBTS) (typical allergenic accelerators) as causative chemicals in 3 cases from children's rubber shoes, ladies' rubber boots and ladies' canvas shoes. These 3 patients reacted to mercaptobenzothiazole-type accelerators including MBT and MBTS. MBT and MBTS were determined in each item of causative footwear by chemical analysis, including extraction by shaking with acetone-chloroform (1:1) mixture at room temperature and determination using reversed-phase high-performance liquid chromatography (RP-HPLC). Subsequently, we identified styrenated phenol (SP), a newly found allergenic antioxidant, as a causative chemical in a case from ladies' canvas shoes. The patient reacted to SP but not to MBT and MBTS, though SP, MBT and MBTS were determined in the causative shoes by gas chromatography (GC), GC-mass spectrometry (GC-MS) and HPLC. We also identified p-tert-butylphenol-formaldehyde resin (PTBP-F-R), (a known allergenic adhesive ingredient) as a causative chemical in a case from ladies' sneakers. The patient reacted to PTBP-F-R but not to p-tert-butylphenol (PTBP), MBT and MBTS. These 4 compounds were determined in the causative sneakers by GC, GC-MS and HPLC. Thus, our studies revealed that not only known allergens, such as MBT, MBTS and PTBP-F-R, but also a newly found one, such as SP, were important causes of allergic contact dermatitis from rubber footwear.

Adhesives↗
PubMed1994

Development of rat one-cell embryos in a chemically defined medium: effects of glucose, phosphate and osmolarity.

Rat one-cell embryos recovered from naturally mated females were cultured in modified hamster embryo culture medium 1 without amino acids. In the presence of 0.4 mmol phosphate l-1 (NaH2PO4), no embryos developed beyond the two-cell stage, regardless of the presence of 5.0 mmol glucose l-1. This inhibition was dose dependent at very low concentrations of phosphate in the medium supplemented with 7.5 mmol glucose l-1 and osmolarity adjusted to 244 mosmol; development to the blastocyst stage was not inhibited at 0.001-0.01 mumol phosphate l-1, but development to the morula and four-cell stages was markedly inhibited at 0.1 and 1.0 mumol phosphate l-1. In the medium without phosphate, glucose did not inhibit or promote development to the morula stage, but adequate concentrations of glucose were necessary for the development of morulae to the blastocyst stage; the percentage of one-cell embryos that developed to the blastocyst stage at 7.5 mmol glucose l-1 (67%) and 10.0 mmol glucose l-1 (60%) were not statistically different from the percentage at 5.0 mmol glucose l-1 (46%), but was significantly greater than the percentage at 2.5 mmol l-1 (33%). When osmolarity of the medium with 5.0 mmol glucose l-1 was varied by adjusting the amount of NaCl added, more (82-98%) of the one-cell embryos developed to the four-cell stage at 212-276 mosmol, but development was greatly inhibited at 304 mosmol. Development to the blastocyst stage was largely dependent on osmolarities; at 244 mosmol, 61% of embryos developed to the blastocyst stage, although this percentage was not significantly different from the percentage (43%) at 264 mosmol.

Animals↗
PubMed1994

Hepatic myelopathy: an unusual neurological complication of advanced hepatic disease.

Encephalopathy is widely known as one of the neurological complications of chronic hepatic disease. Recently, the occurrence of progressive myelopathy in patients with advanced hepatic disease has been well documented and differentiated from encephalopathy. We describe a 76-year-old man with decompensatory liver cirrhosis due to hepatitis C virus infection who suffered from progressive paraplegia. Postmortem examination revealed demyelination of the lateral column of the spinal cord, especially of the thoracic segment. No evidence of spontaneous portosystemic shunts was found. These findings suggest that the patient had been affected with hepatic myelopathy, which is a rare complication of liver cirrhosis.

Aged↗
PubMed1994

Intrahepatic arteriovenous shunting due to hepatocellular carcinoma and cirrhosis, and its change by transcatheter arterial embolization.

OBJECTIVES: To investigate intrahepatic arteriovenous shunt rate due to cirrhosis and hepatocellular carcinoma (HCC), complicated by cirrhosis, and its change after transcatheter arterial embolization. METHODS: The shunt rate was measured by hepatic artery infusion of labeled macroaggregated albumin. Counts were taken over the liver and both lungs for calculation of the shunt rate: cpm in lungs divided by (cpm in liver and lungs) x 100%. RESULTS: The intrahepatic arteriovenous shunt rate of cirrhosis ranged from 6.8% to 16.6% (12.6% +/- 3.4%, mean +/- SD). In HCC, it ranged from 7.2% to 27.1% (16.0% +/- 4.9%, mean +/- SD). The difference between the groups was statistically significant (p < 0.05). When the liver was more than 20% replaced by tumor, the intrahepatic arteriovenous shunt rate was higher than when less than 20% occupied (n = 6, 20.1% +/- 4.8% vs. n = 15, 14.4% +/- 4.0%; p < 0.05). Although the former was significantly different from liver cirrhosis, the latter was not significantly different from the shunt rate observed in liver cirrhosis without HCC. After transcatheter arterial embolization, excluding one patient who developed a visible hepatofugal arterioportal shunt, the mean change in shunt rate between the effective treatment group (n = 9, -2.1% +/- 2.8%, mean +/- SD) and the ineffective treatment group (n = 5, 3.0% +/- 3.3%, mean +/- SD) was statistically significant (p < 0.05). CONCLUSIONS: We found that intrahepatic arteriovenous shunt rate more sensitively detects intrahepatic arteriovenous shunting due to HCC than does angiography alone. Measuring intrahepatic arteriovenous stunt rate may provide useful information regarding response to treatment.

Adult↗
PubMed1993

Abnormal accumulation of phospholipase C-delta in filamentous inclusions of human neurodegenerative diseases.

We have previously demonstrated that an antibody to phosphoinositide-specific phospholipase C (PLC) isozyme, PLC-delta, intensely stained neurofibrillary tangles (NFT) in the brain tissue of Alzheimer's disease (AD). This study was performed to determine if abnormal PLC-delta accumulation might be present in the filamentous inclusions of other neurodegenerative diseases. We found that the anti-PLC-delta antibody stained neuronal inclusions of Pick's disease, progressive supranuclear palsy and diffuse Lewy body disease while the inclusions of idiopathic Parkinson's disease lacked PLC-delta accumulation. These results suggest a possible role for PLC-delta interaction in the formation of intraneuronal filamentous inclusions in human neurodegenerative diseases.

Aged↗