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Biomedical subjects

M Sasaki

Publications and source records attributed to M Sasaki.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1999

Opsonic complement component C3 in the solitary ascidian, Halocynthia roretzi.

The recent identification of two mannose-binding lectin-associated serine protease clones from Halocynthia roretzi, an ascidian, suggested the presence of a complement system in urochordates. To elucidate the structure and function of this possibly primitive complement system, we have isolated cDNA clones for ascidian C3 (AsC3) and purified AsC3 protein from body fluid. The deduced primary structure of AsC3 shows overall similarity to mammalian C3, including a typical thioester site with the His residue required for nucleophilic activation of the thioester. AsC3 has a two-subunit chain structure, and the alpha-chain is cleaved at a specific site near to the N terminus upon activation. Ascidian body fluid contains an opsonic activity which enhances phagocytosis of yeast by ascidian blood cells, and Ab against AsC3 inhibits this opsonic activity. These results indicate that the complement system played a pivotal role in innate immunity by enhancing phagocytosis before the emergence of the vertebrates and well ahead of the establishment of adaptive immunity, which is believed to have occurred at about the time of the appearance of cartilaginous fish.

Amino Acid Sequence↗
PubMed1999

The polymorphisms of DYS388 and DYS392 on the Y chromosome in Japanese and German populations.

The analysis of a genotype survey in Japanese and German populations at the loci DYS388 and DYS392 located on the Y chromosome is reported. The gene diversities of DYS388 were 0.34 and 0.30 in the Japanese and German males, respectively, and six alleles were found in both groups. The gene diversities of DYS392 were 0.65 and 0.64 and the number of alleles was 8 and 9, respectively in the two populations. The distribution of DYS388 alleles in the Japanese population was different from the German population. The allele distribution of DYS392 showed significant differences among Asian populations.

Asian People↗
PubMed1999

A case report of gastric carcinosarcoma with rhabdomyosarcomatous and neuroendocrinal differentiation.

We report herein an unusual gastric carcinosarcoma with rhabdomyosarcomatous and neuroendocrinal differentiation in a 63-year-old Japanese male. The tumor was a pedunculated large polypoid tumor (7 x 6.5 x 3.5 cm) located in the pylorus. Histologically, it invaded to the subserosa and was composed of both adenocarcinomatous and sarcomatous components. Adenocarcinomatous foci generally showed tubular to solid patterns and occupied the parts facing the gastric lumen, while the sarcomatous components showed a generally irregular and solid arrangement. There were transitions between the sarcomatous and carcinoma elements. In addition, carcinoma cells with a cord-like or trabecular arrangement similar to that seen in endocrine carcinoma expressed chromogranin A, and were mainly observed in an intermediate area between the adenocarcinomatous and sarcomatous foci. The sarcomatous areas were mainly composed of spindle cells and occasionally contained a sarcomatous component showing rhabdomyosarcomatous differentiation. This is an interesting case to consider how the variety of cell type appeared in such a type of tumor in the stomach.

Biomarkers, Tumor↗
PubMed1999

Prominent 85-kDa oligomannosidic glycoproteins of rat brain are signal regulatory proteins and include the SHP substrate-1 for tyrosine phosphatases.

The glycoprotein component in rat brain reacting most strongly with Galanthus nivalis agglutinin (GNA) on western blots migrates as an 85-kDa band. GNA identifies mannose-rich oligosaccharides because it is highly specific for terminal alpha-mannose residues. After purification of this 85-kDa glycoprotein band by chromatography on GNA-agarose and preparative gel electrophoresis, binding of other lectins demonstrated the presence of fucose and a trace of galactose, but no sialic acid. Treatment with N-Glycanase or endoglycosidase H produced a 65-kDa band, indicating that it consisted of about one-fourth N-linked oligomannosidic carbohydrate moieties. High-performance anion-exchange chromatography and fluorescence-assisted carbohydrate electrophoresis indicated that the major carbohydrate moiety is a heptasaccharide with the structure Manalpha1-6(Manalpha1-3)Manalpha1-6(Manalpha1-3) Manbeta1-4Glc-NAcbeta1-4GlcNAc (Man5GlcNAc2). Determination of amino acid sequences of peptides produced by endoproteinase digestion demonstrated that this 85-kDa mannose-rich glycoprotein component contained the SHP substrate-1 for phosphotyrosine phosphatases and at least one other member of the signal-regulatory protein (SIRP) family. The unusually high content of oligomannosidic carbohydrate moieties on these receptor-like members of the immunoglobulin superfamily in neural tissue could be of functional significance for intercellular adhesion or signaling.

Amino Acid Sequence↗
PubMed1999

Expression of integrins in squamous cell carcinoma of the oral cavity. Correlations with tumor invasion and metastasis.

Integrins are cell adhesion molecules that mediate the cell to extracellular matrix interactions. We sought to determine whether the integrin expression on tumor cells is associated with invasive and metastatic potential. First, in 8 cell lines of oral squamous cell carcinoma, 4 of which were metastatic in nude mice and 4 of which were not, integrin expression was examined. When these cell lines were cultured in vitro or transplanted into the tongues of nude mice, the metastatic cell lines tended to show a stronger expression of alpha 2, alpha 3, alpha 5, and alpha 6 integrins than did the nonmetastatic cell lines. Second, integrin expression was immunohistochemically examined in 65 biopsy specimens of primary oral squamous cell carcinoma. In invasive or metastatic cases, a marked expression of alpha 2, alpha 3, alpha 5, and alpha 6 integrins was frequently observed. The association of integrin expression with the mode of tumor invasion and nodal involvement was found to be statistically significant. These results suggest that integrin expression is closely associated with tumor invasion and nodal involvement in oral squamous cell carcinoma.

Animals↗
PubMed1999

Surgical treatment of a case of early infantile epileptic encephalopathy with suppression-bursts associated with focal cortical dysplasia.

We report a surgically treated case of early infantile epileptic encephalopathy (EIEE) with suppression-bursts associated with focal cortical dysplasia. Tonic-clonic seizures followed by a series of spasms occurred about a hundred times a day at a few days of age. Interictal electroencephalogram (EEG) revealed a suppression-burst pattern that was predominant in the left hemisphere. Magnetic resonance imaging (MRI) suggested focal cortical dysplasia in the left prefrontal area. Combination therapies with antiepileptic treatments showed only partial efficacy. The patient underwent lesionectomy at age 4 months, after which he gradually showed psychomotor development and a decrease of spasms to 0-2 series daily. In cases of EIEE with focal cortical dysplasia, surgical treatment may have beneficial effects on both psychomotor development and seizure control.

Adrenocorticotropic Hormone↗
PubMed1999

[Magnetoencephalographic and electrocorticographic studies on the epileptogenic focus in a patient with Kojewnikow syndrome].

Partial motor seizures occur, followed after a variable interval by well-localized myoclonic jerks, in the patients with Kojewnikow syndrome, or epilepsia partialis continua. However, the epileptogenic focus remains to be established. We studied the epileptogenic focus of a 17-year-old boy with intractable Kojewnikow syndrome. Interictal EEG, ictal EEG, jerk-locked averaging, and ictal SPECT revealed a left central focus. A giant SEP indicated increased exitability of the primary sensory area. Magnetoencephalogram (MEG) and electrocorticogram identified the epileptogenic focus in the pre- and post-central cortex, indicating involvement of both the primary motor and sensory areas. Surgical treatment was successful. Thus, MEG proved to be the most accurate tool in the presurgical evaluation.

Adolescent↗
PubMed1999

[A case of small cell carcinoma of the stomach with multiple liver and lung metastases successfully treated by combined chemotherapy with cisplatin and etoposide].

We experienced a case of small cell carcinoma of the stomach in which chemotherapy had been markedly effective. A 54-year-old man was admitted to our hospital complaining of hematemesis. Gastric endoscopy showed a type 2 tumor at the lesser curvature of the cardia of the remnant stomach. Total gastrectomy, splenectomy and D2 lymph node dissection were performed. Histopathologically, the tumor was diagnosed as a small cell carcinoma with findings of t 2 n 1 in stage II, and conclusive curability was A. A month after the operation, CT-scan revealed multiple liver and lung metastases, so the patient was treated by combined chemotherapy with cisplatin and etoposide called PVP for three courses every four weeks for small cell lung cancer, which resulted in remarkable reduction of metastases (96% in the liver and 81% in the lung). This result suggests that PVP chemotherapy is effective in the treatment of small cell carcinoma of the stomach as well as the lung.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Heterogeneity of glucose metabolism in corticobasal degeneration.

A positron emission tomography (PET) study on the regional cerebral glucose metabolism (rCMRglc) was performed in six patients with corticobasal degeneration (CBD). The clinical features included asymmetrical parkinsonism with apraxia, were related to the cerebral cortical and basal ganglionic dysfunction. An MRI study showed all cases to have asymmetrical atrophy in the front-parietal cortex contralateral to the dominantly affected limb; however, no case was pathologically verified. A PET study revealed three cases to have asymmetrical glucose hypometabolism in the parietal lobe and thalamus, which was compatible with the results of previous reports. However, two patients demonstrated symmetrical glucose hypometabolism in the frontal lobe, striatum and parietal lobe while one case had a diffuse hypometabolism, in spite of a marked asymmetry of the neurological findings. These results therefore suggest the heterogeneity of the glucose hypometabolism in CBD based on the PET findings.

Aged↗
PubMed1998

Region-specific increase in glutamate release from dorsal horn of rats with adjuvant inflammation.

Glutamate is considered an important pain transmitter and responsible for inflammatory hyperalgesia, but quantitative and topographical changes in glutamate release in the dorsal horn during peripheral inflammation have not been characterized. To address this issue, image analysis with a confocal laser scanning microscope was performed for quantitatively mapping capsaicin-evoked glutamate release from the lumbar cord slice of rats following unilateral adjuvant inoculation to the hind-paw. Capsaicin induced glutamate release from laminae I, II and X in the spinal cord of the adjuvant-treated and untreated sides, without apparent release from laminae III-V. The concentration of released glutamate in laminae I, II and X was higher on the adjuvant-treated side than on the untreated side. The results suggest that adjuvant inflammation increases glutamate release from capsaicin-sensitive primary afferents in laminae I, II and X.

Animals↗
PubMed1998

Combining volume-weighted mean nuclear volume with Gleason score and clinical stage to predict more reliably disease outcome of patients with prostate cancer.

BACKGROUND: Various criteria for patients with prostate cancer have been reported to be of prognostic value, and we have reported that estimates of volume-weighted mean nuclear volume (MNV), developed by Gundersen and Jensen based on a stereological technique, accurately predict the prognosis of prostate cancer. However, all of these studies were conducted on cases in a single institution, and it has remained unclear whether MNV calculations obtained at one institution apply to cases at another institution. In attempting to solve this problem, we made a prognostic index (P.I.) based on data from one hospital, and tested whether these data could be used to predict the prognosis of patients at another hospital. MATERIALS AND METHODS: A retrospective, multivariate prognostic study of 195 patients with prostate cancer, diagnosed at Kyoto University Hospital and treated conservatively, indicated that clinical stage, Gleason score, and MNV were all significantly correlated with the prognosis of patients with prostate cancer. From the relative strengths of these prognostic factors in a multivariate analysis, the following P.I. was constructed: P.I. = Clinical stage x 1.8040 + Gleason score x 1.5245 + MNV x 2.3162 (the constants correspond to the risk ratio estimated by Cox analysis). The P.I. was calculated for 104 patients with prostate cancer diagnosed at Shizuoka City Hospital and treated conservatively for analysis of disease-specific survival. RESULTS: The prognostic index ranged from 3.841-16.142. Using the median value of 12.5 as a cutoff point, a clear separation of cases with poor and favorable prognosis was achieved (P < 0.0001, observation period: 1-167 months). CONCLUSIONS: The results of this study suggest that estimates of MNV can be evaluated at multiple institutions with the use of P.I. calculation. Furthermore, combining estimates of MNV with Gleason score and clinical stage predicts most powerfully disease outcome of patients with prostate cancer.

Aged↗
PubMed1998

Bladder motility and efferent nerve activity during isotonic and isovolumic recording in the cat.

1. Bladder motility and pelvic nerve efferent activity were recorded in anaesthetized cats under isotonic or isovolumic conditions. In isotonic conditions the bladder was connected to a reservoir and fluid entering or leaving the bladder was monitored for 8 min using different heads of pressure (isotonic recording). Under isovolumic conditions fixed volumes were injected into the bladder and pressure changes recorded (micturition contractions). 2. In isotonic conditions, at low pressures the bladder filled to a roughly constant level, and then developed small amplitude oscillatory contractions. At higher pressures, after the initial filling, the bladder contracted, expelling part of its volume. Depending on the pressure this contraction was either sustained or led to a gradual expansion of the bladder. In both cases transient periods of expansion were superimposed. In contrast after an initial slow build up, the efferent nerve activity increased reaching a sustained level of activity during which transient decreases in rate were seen. 3. The firing frequency of the efferent nerve activity during the sustained phase increased as the intravesical pressure was raised until a plateau was reached at high pressures. The plateau pressure (Pplateau) in a bladder was positively correlated with the peak pressure reached by the bladder during micturition contractions under isovolumic conditions, suggesting that micturition contractions were produced by the maximum output of the reflex pathway. 4. Section of the hypogastric nerves had relatively little effect, but additional section of the pelvic nerves abolished the contractile phase of the bladder response to filling, and resulted in continuous filling of the bladder. 5. The transient bladder expansions (duration, 3-33 s) seen when the innervation was intact were closely related to the transient decreases in efferent nerve activity, suggesting involvement of a central inhibitory mechanism. The threshold pressure for triggering transient expansions was similar to the pressure shown to activate myelinated afferent fibres. 6. Under isovolumic conditions the frequency of micturition contractions increased with increasing vesical volume, and the relaxed interval between contractions shortened. This response could also be evoked by stimulation of the central cut end of the pelvic nerves, suggesting that the central inhibitory mechanism could also be active during isovolumic conditions.

Animals↗
PubMed1998

Existence of capsaicin-sensitive glutamatergic terminals in rat hypothalamus.

Capsaicin has been suggested to act not only on thin primary afferents but also on the hypothalamus, but the neurotransmitter(s) of central capsaicin-sensitive neurons are unknown. The present study was conducted to determine whether any central, especially hypothalamic, glutamatergic terminals were sensitive to capsaicin. Capsaicin evoked glutamate release from slices of hypothalamus and lumbar dorsal horn, but not cerebellum. Such capsaicin action was Ca2+ dependent and inhibited by the capsaicin antagonist capsazepine. Vanilloid receptor subtype 1 mRNA was widely distributed in the brain, with a marked level in the hypothalamus and cerebellum, but not in the spinal cord. The results suggest that there are glutamatergic terminals sensitive to capsaicin in the hypothalamus.

Animals↗
PubMed1998

Purification and characterization of the active-site-mutated recombinant human mu-calpain expressed in baculovirus-infected insect cells.

Recombinant human mu-calpain whose active site Cys-115 was substituted with Ser was expressed in insect cells using baculovirus system. The mutant mu-calpain, purified using an affinity-column of calpastatin oligopeptides, had no proteolytic activities of autolysis and caseinolysis. The large subunit of the mutant mu-calpain was processed from the 80 kDa form to the 76 kDa form by the wild type calpain, supporting the intermolecular cleavage mechanism of procalpain during activation. Fluorescence polarization analysis revealed that the mutant mu-calpain retained high affinity toward fluorescein-labeled calpastatin domain 1. Fragmentation of the full-length calpastatin by the wild type calpain was enhanced by pre-incubating the inhibitor with the mutant calpain. The recombinant mutant calpain was suggested to retain the integrity of the high ordered structure of the wild type calpain.

Animals↗
PubMed1998

Cloning, expression analysis, and chromosomal localization of BH-protocadherin (PCDH7), a novel member of the cadherin superfamily.

We have identified a novel member of the cadherin superfamily. Among the members of the superfamily, this protein exhibited the highest overall homology with protocadherin-1 (46-49% identity). Its mRNA was predominantly expressed in the brain and heart. Hence, we named the gene BH-protocadherin (BH-Pcdh) (HGMW-approved symbol PCDH7). BH-Pcdh has an extracellular domain consisting of seven repeats of the cadherin motif (EC 1 to 7). EC2 of BH-Pcdh is unique in having a 55-amino-acid insertion in the middle of the motif. There are three isoforms of BH-Pcdh, denoted -a, -b, and -c, which have different cytoplasmic tails and a 47-amino-acid deletion in the EC2-3 region of BH-Pcdh-c. While only a 9.0-kb message was detected in normal tissues, 4.5- and 9.0-kb mRNA species were seen in the human lung carcinoma cell line A549. Furthermore, only the 4.5-kb mRNA was detected in HeLa cell S3 and human gastric cancer cell lines MKN28 and KATO-III. Southern blot analysis indicated that the BH-Pcdh gene is likely to be conserved among various vertebrates. The BH-Pcdh gene was localized to human chromosome 4p15. Interestingly, 4p15 is a region of loss of heterozygosity in some head and neck squamous cell carcinomas.

Amino Acid Sequence↗
PubMed1998

Relationship between flushing pressure and nitric oxide production in preserved lungs.

BACKGROUND: Nitric oxide (NO) is considered to be one of the endogenous inhibitory factors of ischemic reperfusion injury. In this study, the NO-producing ability of the preserved lung, flushed at various pulmonary artery pressures (flushing pressure), was studied during reperfusion using an ex vivo rabbit lung perfusion model. METHODS: The lungs were flushed with 200 ml of preservation solution with flushing pressures adjusted to 15, 15, 20, and 25 mmHg for groups 1, 2, 3, and 4, respectively (n=5 in each group). In the control group (group 1), the heart-lung block was harvested after flushing and the lungs were assessed without preservation. In the other groups, the harvested blocks were preserved at 8 degrees C for 24 hr and reperfused with homologous blood for pulmonary functional assessment. Pulmonary function was assessed by measuring mean airway pressure, mean pulmonary arterial pressure, partial oxygen tension of pulmonary venous effluent blood, and pulmonary wet-dry weight ratio. The sequential changes in the concentration of NO-related substances (NO-RS) in the serum of reperfused blood were also measured by chemiluminescence. RESULTS: During reperfusion, biphasic increases in NO-RS were observed in all groups. In groups 3 and 4, the increases in NO-RS were significantly lower than those of groups 1 and 2, and pulmonary function deteriorated. CONCLUSION: These data suggest that in order to maintain the endogenous NO-producing ability of preserved lung, the flushing pressure must be less than 20 mmHg.

Animals↗