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Biomedical subjects

M Sasaki

Publications and source records attributed to M Sasaki.

At least 325 records · Page 18Linked to original sources

[Comparison of myelin-forming cells as candidates for therapeutic transplantation in demyelinated CNS axons].

Demyelination of axons resulted in distinct reduction of conduction velocity or block of conduction. Remyelination by transplantation of myelin-forming cells may provide a therapeutic approach for demyelinated diseases. However, which cell type will be the most appropriate candidate for such a cell therapy is not established. To investigate how effective grafted neonatal brain cell (BC) (including oligodendrocyte and astrocyte) isolated from neonatal fronto-temporal lobes, adult olfactory ensheathing cell (OEC) or adult Schwann cell (SC) may be for demyelinated CNS axons in vivo, dorsal columns(DCs) of adult rat spinal cord were demyelinated at Th 11 by X-ray irradiation (day 0) and the injection of ethidium bromide (day 3), and transplanted 5 x 10(4) of BCs, 3 x 10(4) of OECs, or 3 x 10(4) of SCs into the lesion (day 6). Day 28-31, spinal cord were removed and transferred an in vitro recording chamber to record field potentials using glass micropipettes, to investigate conduction properties at 36 degrees. Normal DCs were recorded in same manner. Histological examination revealed that OECs and SCs resulted in substantial SC-like patterns of remyelination to equal degree, BC transplantation resulted in less myelination. The conduction velocities were significantly improved to 4.2 +/- 2.4 m/s(BC, n = 5), 8.5 +/- 3.3 m/s(OEC, n = 6) and 7.7 +/- 1.5 m/s(SC, n = 5), compared to demyelinated axons(1.2 +/- 0.4 m/s, n = 7). A 600 Hz 0.5 sec stimulus train led to an amplitude decrement of 7.1 +/- 7.5% (n = 7) in demyelinated axons. Following transplantation, the amplitude decreased in 31.3 +/- 18.7% (BC, n = 5), 49.9 +/- 19.9% (OEC, n = 6) and 66.2 +/- 11.9% (SC, n = 5). Transplanted OECs and SCs enhanced the remyelination of demyelinated CNS axons, and improved conduction properties were similar, and more effective than that induced from isolated CNS tissue which included oligodendrocyte.

Animals↗

[Results of antimicrobial susceptibilities of strains clinically isolated at 8 institutions in Hiroshima City to major oral antimicrobial drugs, mainly new quinolone drugs. Hiroshima Levofloxacin Susceptibility Surveillance Group].

To evaluate the resistance for major oral antimicrobial agents, mainly new quinolones, we carried out a drug susceptibility surveillance of 3,050 strains of 11 microbial species clinically isolated at 8 institutions such as general hospitals and examination centers in Hiroshima city. 10 antimicrobial agents were used: 3 new quinolone drugs, 5 beta-lactam drugs, minocycline and clarithromycin. Among Gram-positive bacteria, methicillin resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis showed low susceptibility to the new quinolone drugs, while methicillin susceptible Staphylococcus aureus (MSSA) and Streptococcus pneumoniae were highly sensitive to these drugs. Among Gram-negative bacteria, Pseudomonas aeruginosa showed high resistance for the new quinolone drugs, but enteric bacteria and Haemophilus influenzae did not show marked resistance, maintaining almost good sensitivity to these drugs. To reduce the appearance of resistant bacteria, appropriate antimicrobial agents should be selected. Drug susceptibility surveillance in the community will be also important in the future.

4-Quinolones↗

[Remyelination by Schwann cell transplantation for CNS demyelinated axons: functional comparison with developmental myelination].

Transplantation of Schwann cells(SCs) induced remyelination of demyelinated rat dorsal column(DC) axons and improved conduction. To investigate the difference between developmental oligodendrocytic myelination and SC myelination in conductive functions of axons, we compared normally developmental DCs(10 days old, 22-23 days old, and adult rat), demyelinated DCs, and remyelinated DCs by SC transplantation. DCs of adult rats were demyelinated at T 11 by X-ray irradiation and ethidium bromide, and transplanted with SCs(3 x 10(4)) of adult rats. Three weeks later, the spinal cord was removed and pinned in a recording chamber and compound action potentials (CAPs) were recorded, to investigate conduction properties(conduction velocity, amplitude of CAP and response after high frequency stimulation). Normal DCs were recorded in same manner. Following transplantation of SCs, histological examination revealed SC-like patterns of remyelination of demyelinated axons. The conduction velocities of 10 days old DCs(1.7 +/- 3.4 m/s, n = 4) increased early to 8.1 +/- 3.3 m/s(22-23 days old, n = 7) and 12.2 +/- 1.5 m/s (adult, n = 5). After SC transplantation the velocity significantly improved 7.7 +/- 1.5 m/s(n = 5) compared to demyelinated axons(1.2 +/- 0.4 m/s, n = 7), but less than adult. A 600 Hz 0.5 sec stimulus train led to an amplitude decrement of 7.1 +/- 7.5%(n = 7) in demyelinated axons. Following transplantation, amplitude decreased in 66.2 +/- 11.9%(SC, n = 5), same as 22-23 days(71.7 +/- 11.7%, n = 7) old or adult(76.6 +/- 15.6%, n = 6). The recovery properties after high frequency stimulation developed earlier than conduction velocity. Following SC transplantation, the recovery properties improved to that of normal adult, but not conduction velocity. Lower conduction velocity may be due to shorter internode distance of remyelination after transplantation, same as 22-23 days old pups, than normal adult rats. Though anatomical difference and/or time after transplantation influenced the conduction, these result suggested SC remyelination might result in insufficient for conduction velocity.

Animals↗

[Feeding function, blink reflex and MRI in the severely handicapped].

Blink reflexes were studied in 41 patients with severe handicaps, and were correlated with feeding problems and other lower brainstem symptoms such as drooling, an absent gag reflex and stridor. Ventrodorsal diameters of the pons and medulla oblongata on sagittal MRI were also studied in 29 of the cases. The patients were divided into three groups: tube feeding (25 cases), oral feeding (13 cases) and mixed feeding (3 cases). In the tube feeding group, all but three cases showed a prolonged or absent R1 component, and all cases showed prolonged or absent R2 and R2' components. These abnormalities were significantly more frequent in the tube than in the oral feeding group. The patients with drooling, stridor or an absent gag reflex more frequently showed prolonged or absent components than the patients without these symptoms. The brainstem size on MRI was not different between the tube and oral feeding group. These results suggest that the blink reflex, particularly its late components, is a useful indicator for evaluating feeding function and other lower brainstem functions.

Adolescent↗

[Building bridges toward the 21st century].

Just as Rome was not built in a day, there are few great inventions and discoveries that can be made overnight. There are always historical circumstances behind them. Laboratory Automation is not an exception. With the end of World War II in 1945 as a turning point, a large volume of American medicine was introduced all over Japan, and clinical laboratory testing which was imported at the same time has taken root and matured. As a result, we can now carry out prompt and fully automated laboratory testing second to none at many hospital laboratories. In this paper, I recall the development and summarize the expansion by focusing on clinical laboratory automation as it has developed in the latter half of the 20th century in Japan. I would feel amply rewarded for my efforts if this paper proved helpful to the young generation. The clinical laboratory of the 21st century rests on their shoulders.

Automation↗

Effect of exercise training on ANP receptors.

To clarify whether exercise-training affects ANP function, we trained male Wistar rats by treadmill running for nine weeks and measured ANP receptor number and affinity in the kidney, lung and adrenal. We also measured guanylate cyclase activity, by which second messenger cGMP accumulates. The number of adrenal ANP receptor significantly increased after exercise-training. There was no significant difference of affinity for all the organs examined between the training group and the control group. Guanylate cyclase activity tended to decrease in the kidney in the training group. A significant difference was found when the samples were stimulated by C-type natriuretic peptide (CNP). There was no significant difference in guanylate cyclase activity in the lung and adrenal. These findings are consistent with the exercise-induced hypervolemia, but not with the anti-hypertensive role of exercise-training.

Adrenal Glands↗

Cloning and expression profile of mouse and human genes, Rnf11/RNF11, encoding a novel RING-H2 finger protein.

The RING finger (C3HC4-type zinc finger) is a variant zinc finger motif presents in a new family of proteins. A new member of the RING finger family was identified and its cDNA structures were determined in human and mouse. The predicted protein consisting of a 144 amino acid residues is very conservative between the two species and contains a canonical RING-H2 finger motif (C3H2C2) at the carboxyl-terminal region. The genes were designated as RNF11/Rnf11 for RING finger protein 11. A single 2.4-kb transcript of mouse Rnf11 was ubiquitously expressed in various fetal and adult mouse tissues by the Northern blot analysis. The human RNF11 gene was mapped on chromosome 1p31-p32 region, where frequent alterations have been observed in T-cell acute lymphoblastic leukemia.

Amino Acid Sequence↗

Characterization of the human dihydropyrimidinase-related protein 2 (DRP-2) gene.

The genes within the dihydropyrimidinase-related protein (DRP) family, were originally identified in humans by their homology to dihydropyrimidinase (DHP). Four members of this gene family, DRP-1, -2, -3 and -4, are expressed mainly in the fetal and neonatal brains of mammals and chickens, and have been implicated as intracellular signal transducers in the development of the nervous system. We isolated the human DRP-2 gene, and determined its transcriptional start site and exon/intron organization. The gene spanned more than 62 kb, and contained 14 exons with lengths ranging from 62 bp to 2606 bp. The transcriptional start site was determined by an RNase protection assay and 5' rapid amplification of cDNA ends (RACE), and a highly GC-rich promoter was identified that contained possible regulatory elements such as a TATA box, CAAT box and three GC boxes. Comparison of the phase and position of intron insertions within the human DRP-2 gene with those within DRP-1, DHP and two Caenorhabditis elegans DRP/DHP homologs, indicated that DRPs are more conserved in their exon/intron organization than DHP.

Amidohydrolases↗

cDNA cloning, tissue expression, and chromosomal assignment of a mouse gene, encoding a 127 kDa UV-damaged DNA binding protein which is defective in XPE cells.

A subset of xeroderma pigmentosum (XP) group E cells lack a factor of the UV-damaged DNA binding activity. Both 127 kDa and 48 kDa proteins have been reported to be responsible for the binding activity. A cDNA for the 127 kDa UV-damaged DNA-binding protein (p127-Ddb1) was isolated from a mouse fetal brain full length-enriched cDNA library, and an open reading frame of 1140 amino acids was identified. Reverse transcription-coupled polymerase chain reaction (RT-PCR) showed that mouse Ddb1 messenger is ubiquitously expressed in adult tissues as well as in embryo's. The gene was mapped to near the public locus D19Mit22 region of mouse chromosome 19.

Amino Acid Sequence↗

Primary progressive aphasia presenting as conduction aphasia.

We report a case of a woman with primary progressive aphasia (PPA) who presented with conduction aphasia. A 60-year-old, right-handed, Japanese female suffering from progressive aphasia had difficulty in repeating words and phrases. She displayed phonemic paraphasias but had preserved comprehension and had no cognitive or behavior disorder for more than 6 years after the onset of the condition. She was able to continue to work successfully and to perform all her normal daily activities. T1-weighted magnetic resonance imaging revealed minute dilatation of the left inferior horn and sulci in the left hemisphere, and positron emission tomography revealed mild hypometabolism in the left supramarginal gyrus and its surrounding areas. Therefore, she was diagnosed as suffering from PPA presenting as conduction aphasia. We believe that the progressive conduction aphasia of the patient belongs to one of the fluent forms of PPA, and the ability to continue normal work along with the clinical portrayal of preserved memory and cognition skills may be features of a form of PPA presenting as conduction aphasia.

Aphasia, Conduction↗

Visual hallucinations and regional cerebral metabolism in dementia with Lewy bodies (DLB).

To investigate the neurobiological bases of visual hallucinations in dementia with Lewy bodies (DLB), regional cerebral glucose metabolism was compared among three patient groups; DLB with visual hallucinations, DLB without visual hallucinations and Alzheimer's disease (AD) without visual hallucinations. The regional metabolism was significantly lower in both DLB groups than in the AD group in the primary visual area and the posterior temporal, parietal and lateral occipital association areas. The hypometabolism in the right posterior temporal and parietal areas was significantly milder in DLB with visual hallucinations than in DLB without hallucinations. The hypometabolism in the primary visual cortex and the relatively preserved metabolism in the right temporoparietal association cortices may be associated with the occurrence of visual hallucinations in DLB patients.

Aged↗

Molecular characteristics of poorly differentiated adenocarcinoma and signet-ring-cell carcinoma of colorectum.

In a series of 45 poorly differentiated adenocarcinomas (por) and 7 signet-ring-cell carcinomas (sig) of the colorectum, K-ras gene mutation, p53 immunostaining and microsatellite instability (MSI) were analyzed for a comparison with 46 cases of colorectal carcinomas of the well or moderately differentiated type (well/mod). In addition, the mutations of simple repeated sequences in the transforming-growth-factor-beta type-II receptor (T beta R-II) gene and the BAX gene were analyzed as possible targets for DNA replication errors. Mutation of the K-ras gene in the por, sig and well/mod specimens was detected in, respectively, 22%, 11% and 48%, positive immunostaining for p53 in 41.8%, 28.6% and 60.3%, and MSI in 36%, 30% and 4%. Frameshift mutation of the T beta R-II gene was detected in 27.5% of the por and none of the sig specimens, while corresponding figures for mutation of the BAX gene were 15.7% and 0%. Significant differences between the por and well/mod tumors were found in the occurrence of K-ras mutation at codons 12 and 13, and MSI. Clinicopathologically, the tumor status of por with MSI was found to significantly correlate with the tumor's location in the proximal colon. In cases without MSI and sig, no frameshift mutation of either the T beta R-II or the BAX gene was found. These results suggest that poorly differentiated and signet-ring-cell carcinomas have a genetic background different from that of well or moderately differentiated carcinomas of the colorectum, and that DNA-replication error is at least partly involved in the carcinogenesis of these specific types of colorectal carcinomas.

Adenocarcinoma↗