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Biomedical subjects

M Mimura

Publications and source records attributed to M Mimura.

At least 19 recordsLinked to original sources

Constant involvement of the Betz cells and pyramidal tract in amyotrophic lateral sclerosis with dementia: a clinicopathological study of eight autopsy cases.

We investigated clinicopathologically pyramidal signs, including hyperreflexia, Babinski sign, and spasticity, and the involvement of the primary motor cortex and pyramidal tract, in eight Japanese autopsy cases of amyotrophic lateral sclerosis (ALS) with dementia. Pyramidal signs were observed in seven (88%) of the eight autopsy cases. Hyperreflexia and Babinski sign were evident in seven (88%) and three (38%) patients, respectively, but spasticity was not observed in any of the eight patients. Loss of Betz cells in the primary motor cortex was evident in the seven cases in which this structure was examined. Astrocytosis in the fifth layer of the primary motor cortex was noticed in three cases. In all eight cases, involvement of the pyramidal tract was obvious in the medulla oblongata, but no involvement of the pyramidal tract was found in the midbrain. Involvement of the pyramidal tract in the spinal cord, particularly of large myelinated fibers, was observed in all six cases in which the spinal cord was examined. In ALS with dementia, pyramidal signs were shown to be present more frequently than previously believed, and the clinicopathological correlation between pyramidal signs and involvement of the pyramidal tract was obvious. Constant involvement of Betz cells and the pyramidal tract in ALS with dementia has not been reported. Our clinicopathological findings may make a contribution to the understanding of the clinicopathological hallmarks of this disorder. Furthermore, we believe that this study will also contribute to the elucidation of the nosological status of ALS with dementia.

Adult↗

Palinopsia and perilesional hyperperfusion following subcortical hemorrhage.

We report a patient who exhibited transient palinopsia and visual hallucinations. Disturbances initially included an auditory component and increasingly were localized to the left visual field. These events occurred during recovery from a right subcortical hematoma with left homonymous hemianopia. Single-photon emission computed tomography (SPECT) demonstrated extensive perilesional hyperperfusion involving parts of the right parietal, temporal, and occipital cortex. Perilesional hyperperfusion disappeared as the visual abnormalities diminished. We believe that excitatory neuronal activation in perilesional cortex during recovery contributed importantly to the transient abnormal perceptions.

Cerebral Hemorrhage↗

Rational design, discovery, and synthesis of a novel series of potent growth hormone secretagogues.

In the joint experimental and computational efforts reported here to obtain novel chemical entities as growth hormone secretagogues (GHSs), a small database of peptides and non-peptides known to have GHS activity was used to generate and assess a 3D pharmacophore for this activity. This pharmacophore was obtained using a systematic and efficient procedure, "DistComp", developed in our laboratory. The 3D pharmacophore identified was then used to search 3D databases to explore chemical structures that could be novel GHSs. A number of these were chosen for synthesis and assessment of their ability to release growth hormone (GH) from rat pituitary cells. Among the compounds tested, those with a benzothiazepin scaffold were discovered with micromolar activity. To facilitate lead optimization, a second program, a site-dependent fragment QSAR procedure was developed. This program calculates a library of chemical and physical properties of "fragments" or chemical components in a known pharmacophore and determines which, if any, of these properties are important for the observed activity. The combined use of the 3D pharmacophore and the results of the site-dependent fragment QSAR analysis led to the discovery and synthesis of a novel series of potent GHSs, a number of which had nanomolar in vitro activity.

Animals↗

Corticobasal degeneration presenting with nonfluent primary progressive aphasia: a clinicopathological study.

A 62-year-old woman initially presented with slowly progressive nonfluent aphasia with minimal intellectual involvement. Echolalia and personality change were prominent whereas parkinsonian features and signs suggesting parietal lobe dysfunctions were not present. The patient's language deficit was consistent with transcortical motor aphasia. She did not manifest extrapyramidal signs. The patient was diagnosed as having Pick's disease or frontal lobe dementia. She died at age 65, 2 years and 9 months following disease onset. Neuropathological findings including cytoskeletal abnormalities, however, were clearly distinct from those of classical Pick's disease and were consistent with those reported in corticobasal degeneration (CBD). The distribution of her cortical lesions was accentuated in the frontal language-related area. The clinical manifestations in CBD are diverse, and primary progressive nonfluent aphasia should be considered as an initial symptom of CBD. Neuropathological examination of such patients should include cytoskeletal abnormality studies.

Aphasia, Primary Progressive↗

Malignant melanoma in the oral region: ultrastructural and immunohistochemical studies.

Malignant melanoma in the oral region is reviewed in its clinicopathological aspects. Clinically the melanomas were classified into five types; however, there were no histopathological differences according to these clinical types. Electron microscopic observation of the melanomas and primary culture cells derived from oral malignant melanoma revealed that, in patients whose prognoses were relatively good, many mature-stage melanosomes were found. Immunohistologically, there was a positive reaction for transferrin receptor and the expression of pRb2/p130 was found in only 2 of 13 patients, who are still alive after periods of over 14 years. The radiosensitivity of a cell line derived from human oral malignant melanoma was greater than that in cell lines derived from human cutaneous melanoma and with radiation, the number of melanosomes increased. There are very few clinical cases of oral malignant melanoma and very few cell lines derived from oral malignant melanoma, and so findings in these patients and these cell lines should be accumulated in order to clarify the biological behavior of oral malignant melanoma.

Cell Line↗

Expression of Rb, pRb2/p130, p53, and p16 proteins in malignant melanoma of oral mucosa.

We previously reported that pRb2/p130 gene, one of the Rb family members, was immunohistochemically abundantly expressed in well-differentiated oral squamous cell carcinomas, whereas in undifferentiated ones the expression was low. Oral malignant melanoma is extremely rare, however the prognosis is poor because it tends to locally invade tissue or metastasize and its biological behavior appears to be different from cutaneous malignant melanoma. The present study dealt with the expression of pRb2/p130, Rb, p53, and p16 in 13 cases of malignant melanoma of oral mucosa as revealed by immunohistochemical staining. The stage classification of the 13 patients was as follows; stage II: eight patients, stage III: three patients, and stage IV: two patients. pRb2/p130 was expressed in only two stage II-cases, neither of which have shown any evidence of recurrence or metastasis for over 14 years. Positive staining for Rb was found in three cases consisting of one stage II-case, one stage III-case, and one stage IV-case. p53 was expressed in two cases, one a stage II and the other a stage IV. Positive staining for p16 was found in seven cases consisting of four stage II-cases, two stage III-cases, and one stage IV-case. pRb2/p130 may be inversely correlated with the malignancy of oral malignant melanoma, but further study is needed.

Aged↗

[Generalized tonic-clonic seizure induced by propofol in a patient with epilepsy].

A 47-year-old female was scheduled for ulnar osteotomy under general anesthesia combined with brachial plexus block. She had a history of symptomatic epilepsy due to subarachnoid hemorrhage. Immediately after giving 100 mg bolus of propofol to the patient, she developed generalized convulsion similar to a grand mal. The seizure was suppressed by the administration of thiamylal. After that no further convulsive attack occurred. Although it has been known that propofol has anticonvulsive properties, there have been several reported cases of seizure following the administration of propofol. Further studies are needed to clarify the mechanism of seizure induced by propofol in the patients with epilepsy.

Anesthesia, General↗

Microvilli and desmosomes of squamous cell carcinoma cells in tongue carcinoma related to regional lymph node metastasis: ultrastructural and immunohistochemical studies with transferrin receptor.

Squamous cell carcinomas of the tongue (n = 49), consisting of 21 cases with cervical lymph node metastasis and 28 nonmetastatic cases, were examined by electron microscopy with special emphasis on tumor cell attachment. No difference of tumor size (T classification) or pathological findings between the metastatic group and the nonmetastatic group was found. The metastatic cases had numerous microvilli and a small number of desmosomes regardless of the width of the intercellular spaces. The nonmetastatic cases had few microvilli in relatively wide intercellular spaces, or, in the cases in which numerous microvilli were present in the narrow intercellular spaces, the tumor cells were connected by a large number of desmosomes. Transferrin receptor, which is a marker of cell proliferation, was localized in the cell membrane by immunohistochemistry and especially in microvilli by immunoelectron microscopy. It is suggested that microvilli might be related to the proliferation and the metastasis of squamous cell carcinoma cells.

Adult↗

Investigation of titanium leak to bone tissue surrounding dental titanium implant: electron microscopic findings and analysis by electron diffraction.

This study investigated the tissue response associated with dental titanium implants. The mandibular third and fourth premolars and first molar of three adult beagle dogs were extracted bilaterally. Healing was then allowed for 3 months. Six titanium implants were placed in the mandibles of a dog. Three weeks after the implantation, mandibular sections containing the implants were retrieved with the use of a bone saw and investigated by light and electron microscopy, X-ray microanalyzer, and electron diffraction. Scanning electron microscopic observation showed titanium particles on the implant-bone interface, and investigation by microanalyzer revealed titanium not only on the implant-bone interface but also in the bone tissue. Transmission electron microscopic observation and investigation by electron diffraction showed titanium in the bone matrix and cells other than macrophages. In this study, titanium particles from the dental implant were recognized morphologically in the surrounding bone tissue. Thus, study of the influence of titanium particles on the human body is needed.

Animals↗

Time estimation by patients with frontal lesions and by Korsakoff amnesics.

We studied time estimation in patients with frontal damage (F) and alcoholic Korsakoff (K) patients in order to differentiate between the contributions of working memory and episodic memory to temporal cognition. In Experiment 1, F and K patients estimated time intervals between 10 and 120 s less accurately than matched normal and alcoholic control subjects. F patients were less accurate than K patients at short (< 1 min) time intervals whereas K patients increasingly underestimated durations as intervals grew longer. F patients overestimated short intervals in inverse proportion to their performance on the Wisconsin Card Sorting Test. As intervals grew longer, overestimation yielded to underestimation for F patients. Experiment 2 involved time estimation while counting at a subjective 1/s rate. F patients' subjective tempo, though relatively rapid, did not fully explain their overestimation of short intervals. In Experiment 3, participants produced predetermined time intervals by depressing a mouse key. K patients underproduced longer intervals. F patients produced comparably to normal participants, but were extremely variable. Findings suggest that both working memory and episodic memory play an individual role in temporal cognition. Turnover within a short-term working memory buffer provides a metric for temporal decisions. The depleted working memory that typically attends frontal dysfunction may result in quicker turnover, and this may inflate subjective duration. On the other hand, temporal estimation beyond 30 s requires episodic remembering, and this puts K patients at a disadvantage.

Adult↗

[Support for patients with a respirator at home].

Five patients with a respirator were managed at home by staff from our visiting nurse station. One patient has been at home for 4 years after discharge. She is 60 years old. Her disease was striatonigral degeneration. Five years ago she could not breathe because of her disease and breathing with a respirator was started. However, she and her family wanted her to be at home. We respected their wish, and helped her stay at home. She has maintained a good condition with nursing at home, and her QOL is high.

Female↗

[A case of moyamoya disease presenting with geographic mislocation, person misidentification and fantastic confabulation].

A 52-year-old woman presented with geographical mislocation (misidentification for place), person misidentification and fantastic confabulation as a result of cerebral infarction. Head MRI demonstrated a focal lesion in the right frontal lobe. Cerebral angiogram demonstrated occlusion in the circle of Willis with moyamoya vessels. The neuropsychological examination revealed memory impairment and frontal lobe dysfunction. The patient's misidentification for place and person as well as confabulation lasted for 1.5 months since admission, then gradually disappeared. We speculate that there existed a common mechanism for these three symptoms; i.e., misidentification and confabulation were based upon the impaired interpretation of the small events and partial objects in the surrounding circumstances, which might interfere with the appropriate integration and judgments of the outside information in general. The impaired monitoring and frontal dysfunction caused by the right frontal lesion appeared to be responsible for causing her deficits.

Brain↗

Disappearance of serum HCV-RNA after short-term prednisolone therapy in a patient with chronic hepatitis C associated with autoimmune hepatitis-like serological manifestations.

We report a 70-year-old woman with chronic hepatitis C associated with autoimmune hepatitis (AIH)-like serological manifestations, in whom elimination of hepatitis C virus (HCV) was observed after corticosteroid treatment. The patient was infected with HCV, genotype Ib, but had several laboratory findings, such as markedly elevated serum gamma-globulin and IgG, characteristic of AIH, as well as a high titer of an anti-nuclear antibody. An ultrasound (US)-guided liver biopsy disclosed chronic active hepatitis F3. Corticosteroid worsened her liver function test results and raised amounts of HCV-RNA in the serum. Withdrawal of the corticosteroid led to prompt normalization of transaminase levels and the disappearance of serum HCV-RNA, determined by reverse transcription-polymerase chain reaction (RT-PCR). For 4 years, up to the time of this study, her transaminase values have been normal and HCV viremia was not detected by repeated RT-PCR. We believe this to be the first reported case in which eradication of HCV was achieved by corticosteroid therapy alone, without the introduction of interferon.

Aged↗

Electron-microscopic study of the bactericidal effect of OPB-2045, a new mono-biguanide disinfectant produced from biguanide group compounds, against Pseudomonas aeruginosa.

The bactericidal activity of OPB-2045 (1-(3,4-dichlorobenzyl)-5-octylbiguanide monohydrochloride hemihydrate) at several concentrations against Pseudomonas aeruginosa IFO 13275 was investigated morphologically by transmission and scanning electron microscopy. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of OPB-2045 against P. aeruginosa were the same, at 12.5 microg mL(-1), suggesting that it may be a suitable disinfectant for use in the medical field. Test bacteria were treated at concentrations of one half the MIC value (6.25 microg mL(-1)), the MIC value (12.5 microg mL(-1)), twice the MIC value (25 microg mL(-1)) or ten times the MIC value (125 microg mL(-1)) at 37 degrees C for 30 min or 6 h and the cells were then examined by transmission and scanning electron microscopy. The cell damage evident after 6h incubation was greater than observed after 30 min incubation. Especially, at one half the MIC, no cell damage was evident after 30 min incubation, but damaged cells were observed after 6 h incubation. The proportion of empty cells of P. aeruginosa increased as the concentration of added disinfectant was increased, and the release of intracellular components was also recognized. These results suggest that OPB-2045 acts on the cell membrane and cell wall of P. aeruginosa, and destroys their integrity at the level of the MIC (MBC). With the increase in OPB-2045 concentration and the increase in reaction time, the bactericidal effect increased markedly. Agglutination of the cells was observed at high concentrations of OPB-2045. This indicates that the bactericidal effect at high concentrations of OPB-2045 differs from that at low concentrations. A clear cell-damaging effect against the test strain was recognized which was dependent on the OPB-2045 concentration and the incubation time. From experiments concerning the relationship between the number of surviving bacteria and MIC values in soybean casein digest broth, the decrease in bacterial numbers was found to be dependent on the OPB-2045 concentration. We conclude that it would be a useful contribution to the medical field to supply a new disinfectant to be employed in preventive countermeasures against infection caused by pathogenic bacteria.

Anti-Infective Agents, Local↗

Visible changes in lesion borders on CT scan after five years poststroke, and long-term recovery in aphasia.

This study examined 12 aphasia patients at approximately 1 year poststroke (Time 1) and again at 5-12 years poststroke (Time 2) with language testing and CT scan. Significant increases in naming scores, and phrase length in nonfluent speech were observed after 5 years poststroke. Significant expansion in visible lesion borders (lesion size) was observed after 5 years poststroke; an increase in lesion size of > 1% was present in 9/12 cases (75%). Not one case had a second stroke. Thus, it appears that even though lesion expansion may occur after 5 years poststroke, as long as this expansion is unilateral and gradual, it has no adverse effect on language, and in fact, continued recovery in naming and nonfluent speech may also occur. Long-term recovery patterns in aphasia which may be associated with brain reorganization deserve further study, especially with functional brain imaging techniques.

Aged↗

A missense mutation in the CD38 gene, a novel factor for insulin secretion: association with Type II diabetes mellitus in Japanese subjects and evidence of abnormal function when expressed in vitro.

Cyclic adenosine 5'diphosphate-ribose (cADPR) is thought to have a second messenger role in insulin secretion through mobilisation of Ca2+. As human lymphocyte antigen CD38 has both ADP-ribosyl cyclase and cADPR hydrolase activity, it may be important in glucose-induced insulin secretion in islets. Thirty one randomly selected Japanese patients with Type II diabetes mellitus who had first-degree and/or second-degree relative(s) with Type II diabetes mellitus were screened for mutations of this gene using single-stranded conformation polymorphism. Two variant patterns in exon 3 and exon 4 of the CD38 gene were identified. The variant in exon 3 resulted in an amino acid substitution from Arg140 (CGG) to Trp (TGG). The Arg140Trp mutation was observed in 4 of 31 patients, and allele frequencies were significantly different in patients and the control subjects (p = 0.004). One patient with this mutation has two missense mutations on beta cell/liver glucose transporter (GLUT2) gene; her mother, who has impaired glucose tolerance, also has this mutation on the CD38 gene and one missense mutation on the GLUT2 gene. Enzyme activity studies using COS-7 cells expressing the Arg140Trp mutation showed a reduction in ADP-ribosyl cyclase and cADPR hydrolase activity of around 50%. The Arg140Trp mutation on CD38 thus appears to contribute to the development of Type II diabetes mellitus via the impairment of glucose-induced insulin secretion in the presence of other genetic defects.

ADP-ribosyl Cyclase↗