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Biomedical subjects

M Sakamoto

Publications and source records attributed to M Sakamoto.

At least 199 records · Page 11Linked to original sources

[A case of common variable immunodeficiency that responded to long-term erythromycin chemotherapy].

A 32-year-old woman with common variable immunodeficiency (CVID) accompanied by sinopulmonary infection was evaluated for purulent sputum, cough, and nasal obstruction that did not respond to regular intravenous immunoglobin (IVIG) infusion. Chest X-ray films revealed bronchiectasis affecting both lung bases, and a bacteriological examination of sputum was positive for Pseudomonas aeruginosa. Long-term chemotherapy with erythromycin (EM) was started, and the patient's respiratory symptoms gradually subsided. Sinopulmonary infection is the dominant clinical complication in patients with CVID. This case suggested that long-term EM chemotherapy is useful for the treatment of IVIG-refractory sinopulmonary infection associated with CVID.

Adult↗

Macroscopic intrabiliary growth of liver metastases from colorectal cancer.

BACKGROUND: The clinicopathologic features of colorectal liver metastases that invade the bile duct were evaluated. METHODS: From 1992 to 1996, 149 patients who underwent a first hepatic resection were studied for a total of 377 colorectal liver metastases. Twenty-one second hepatic resections in these patients were also analyzed. RESULTS: Bile duct invasion was histologically observed in 62 (42%) of 149 patients with first colorectal liver metastasis. Eighteen patients (12%) had gross extension of the tumor in the bile duct ranging from 4 mm to 42 mm (median 17.0 mm). Histologically, two thirds (12 of 18) of the tumors with macroscopic bile duct invasion were well-differentiated adenocarcinomas with a tendency for less vascular involvement. The actuarial 3- and 5-year survivals were 62% and 57% for patients with no bile duct invasion, 56% and 48% for patients with microscopic bile duct invasion, and 94% and 80% for patients with macroscopic bile duct invasion. The 5-year survival rate was better for patients with macroscopic bile duct invasion than for those with only microscopic (P = .02) or no bile duct invasion (P = .03). In a multivariate analysis, macroscopic bile duct invasion was an independent prognostic variable for favorable outcome after hepatic resection. CONCLUSIONS: Macroscopic bile duct invasion of colorectal liver metastases may reflect an indolent biologic behavior, warrants an aggressive surgical approach, and confers a better prognosis.

Adenocarcinoma↗

Reduced p27Kip1 expression in hepatocellular carcinomas.

This study was designed to determine whether changes in p27Kip1 expression are involved in human hepatocarcinogenesis. We examined the p27Kip1 mRNA expression in hepatocellular carcinomas and surrounding non-cancerous liver tissue samples from 21 patients using a reverse-transcriptase polymerase chain reaction assay. The mean p27Kip1 mRNA expression levels (ratio of p27Kip1/beta-actin mRNA) were significantly lower in hepatocellular carcinomas than in non-cancerous liver tissues (0.49 +/- 0.24 versus 0.57 +/- 0.22, P < 0.05). p27Kip1 mRNA expression was reduced in 11 (52%) of the 21 hepatocellular carcinomas when compared with the surrounding non-cancerous liver tissues. These findings suggest that reduced p27Kip1 expression may be at least partly responsible for human hepatocarcinogenesis.

Adult↗

Evidence for the archaebacterial-type conformation about the bond between the beta-ionone ring and the polyene chain of the chromophore retinal in chlamyrhodopsin.

Previous studies using retinal analogs (Wada, A., Sakai, M., Kinumi, T., Tsujimoto, K., Yamauchi, M. and Ito, M. (1994) J. Org. Chem. 59, 6992-6997; Wada, A., Sakai, M., Imamoto, Y., Shichida., Y., Yoshizawa, T. and Ito, M. (1993) Chem. Pharm. Bull. 41, 793-795) revealed that both retinochrome and visual pigments share a common chromophoric conformation in which the ring region of retinal is twisted ca. 50 degrees with respect to the plane of the polyene chain, suggesting a highly conserved 6-s-cis conformation throughout rhodopsin-like pigments in animals. By contrast, 6-s-trans conformation was commonly observed or suggested in archaebacterial rhodopsins examined thus far. Here we have reconstituted in vivo both the photoreceptor for photobehavioral responses of the unicellular alga Chlamydomonas reinhardtii and the second archaeal sensory photoreceptor phoborhodopsin from a series of retinal analogs. Results exclusively point to the conclusion that in both photoreceptors retinal has the coplanar 6-s-trans conformation, though recent molecular cloning studies revealed no homology between Chlamydomonas photoreceptor (chlamyrhodopsin) and archaeal rhodopsins.

Animals↗

Beta-catenin mutation in carcinoma of the uterine endometrium.

Beta-catenin forms complexes with Tcf and Lef-1 and functions as a transcriptional activator downstream of the Wnt signaling pathway. Activation of the pathway by stabilization of beta-catenin has been shown to be important in the development of colorectal carcinoma, which is mainly caused by inactivating mutations of the adenomatous polyposis coli tumor suppressor gene or by activating mutations in exon 3 of the beta-catenin gene. Here, we analyzed mutations in exon 3 of the beta-catenin gene in endometrial carcinoma cases in which loss of heterozygosity at the adenomatous polyposis coli tumor suppressor gene locus has been rarely reported. We found that 10 of 76 cases had beta-catenin gene mutations. All mutations identified were single-base missense mutations on serine/threonine residues (codons 33, 37, 41, and 45), altering the glycogen synthase kinase-3beta phosphorylation consensus motif, which participates in the degradation of beta-catenin. To determine whether these beta-catenin mutations actually led to stabilization of this protein, expression of beta-catenin was analyzed immunohistochemically, and 9 of 10 cases with the beta-catenin mutation and 20 of 66 cases without it showed accumulation of beta-catenin in the cytoplasm and/or nucleus. In total, 38% of cases showed accumulation of beta-catenin. These data indicate that stabilization of beta-catenin due to mutations in exon 3 of the beta-catenin gene and other mechanisms may have an important role in development of endometrial carcinomas.

Adult↗

Comparison of ipsilateral activation between right and left handers: a functional MR imaging study.

We used fMRI to compare the ipsilateral activation in the sensorimotor region (SMR) during dominant and non-dominant hand motor tasks between right and left handers. In right handers, the ipsilateral activation was significantly greater during non-dominant (left) hand task than dominant (right) hand task, while in left handers, it showed no significant difference. The ipsilateral activation was most pronounced in the precentral subregion (presumably corresponding to the premotor area) during either hand task in both groups. We conclude that the different patterns of ipsilateral activation might be mainly explained by the hemispheric dominance. The skill of the hand and complexity of tasks may be related to the predominant activation of the premotor area.

Adult↗

Needle tract implantation of hepatocellular carcinoma after percutaneous ethanol injection.

BACKGROUND: Percutaneous ethanol injection (PEI) therapy currently is widely used for small hepatocellular carcinoma (HCC). However, only limited information is available regarding needle tract implantation after PEI treatment. METHODS: Records of HCC patients who underwent PEI between March 1990 and April 1997 at the National Cancer Center Hospital (n = 177) were reviewed to clarify the incidence, risk factors, and outcome of needle tract implantation of HCC. RESULTS: PEI was performed for 348 HCC patients with a median tumor size of 20 mm. Needle tract implantation was found in 4 patients (10, 13, 15, and 46 months, respectively, after PEI). The size of the PEI-treated HCC tumors in these patients was 20, 27, 28, and 30 mm, respectively, in greatest dimension. All tumors were enhanced in the early phase on dynamic computed tomography (CT), and were found to have moderate tumor cell differentiation on biopsied specimens. Of the four implanted tumors, three were resected and the remaining tumor was treated with extrabeam radiotherapy. At last follow-up, 2 of the 4 patients had died (1 of variceal bleeding 60 months after PEI and the other from cancer 61 months after PEI) and 2 were still alive (14 and 20 months, respectively, after PEI) with no evidence of active tumor. CONCLUSIONS: Needle tract implantation after PEI is not unusual, especially when HCC tumors are > or =2 cm in greatest dimension, enhanced in the early phase on dynamic CT, and/or moderately differentiated on biopsied specimens.

Administration, Cutaneous↗

Widespread neuronal degeneration in rats following oral administration of methylmercury during the postnatal developing phase: a model of fetal-type minamata disease.

The neurotoxicity of methylmercury (MeHg) treatment during the postnatal developing phase in rats was studied. Rats on postnatal day 1 were orally administered 5 mg/kg/day methylmercury chloride (MMC) for more than 30 consecutive days. Body weight loss began 26 days after MMC was administered, and severe paralysis of the hind-limbs and unsteadiness appeared subsequently. Histopathologically, the widespread neuronal degeneration was observed in the cerebral neocortex, neostriatum, red nucleus, brainstem, cerebellum and spinal dorsal root ganglia on day 32. The widespread distribution of the lesions was quite similar to that in fetal cases of MeHg intoxication in Minamata, Japan. These findings suggest that MMC treatment during the postnatal development phase in rats produce a good model of fetal-type Minamata disease.

Animals↗

Favorable strategy for the ostial lesion of the left anterior descending coronary artery: influence on narrowing of circumflex coronary artery.

We examined the effectiveness of Palmaz-Schatz (P-S) stent and directional coronary atherectomy (DCA) in ostial lesions of left anterior descending arteries (LAD). The P-S stent was implanted in 11 cases at LAD ostial lesions, and DCA was performed in 13 cases. Percent stenosis and vessel diameter at the target site and the ostium of the circumflex coronary artery (LCX) were measured before and after the procedure. The initial success rate was 100% in both groups. No major complication occurred. LAD ostial lesions were improved from 81.3+/-3.4% to -8.1+/-5.7% by P-S stent and from 82.8+/-2.6% to -2.7+/-3.9% by DCA. LCX ostial vessel diameter was not changed by DCA (from 3.0+/-0.2 mm to 3.1+/-0.3 mm); however, it was significantly decreased by P-S stent (from 2.9+/-0.2 mm to 2.6+/-0.2 mm, P < 0.01). When the angle of LAD and LCX was < or = 80 degrees from the view of RAO 30 degrees and Caudal 30 degrees, the LCX ostium was significantly narrowed by stenting at LAD ostium (P < 0.01). These findings indicate that both the P-S stent and DCA are effective and safe therapies for LAD ostial lesions in cases with LAD-LCX angle > 80 degrees. In cases with LAD-LCX angle < or = 80 degrees, however, DCA is a favored therapy rather than P-S stenting to avoid narrowing of the LCX ostium.

Atherectomy, Coronary↗

Successful predilation of a resistant, heavily calcified lesion with cutting balloon for coronary stenting: a case report.

A 65-year-old man with a restenotic lesion of the mid LAD was scheduled for Wiktor stent placement. The IVUS revealed circumferential severe calcification. Two conventional, non-compliant angioplasty balloons inflated to high pressures failed to achieved sufficient dilatation and both ruptured. At this point, we selected high pressure inflation of the Cutting Balloon. The Cutting Balloon achieved adequate dilation for stenting and proved to be useful in predilating a circumferential, heavily calcified lesion.

Aged↗

Early hepatocellular carcinoma as an entity with a high rate of surgical cure.

Early hepatocellular carcinoma (HCC) has been defined as a well-differentiated cancer containing Glisson's triad, but it remains unknown whether this lesion is curable. We prospectively studied 70 patients (enrolled from 1,172 referrals between 1982 and 1991) who had a diagnosis of a single HCC 2 cm or less in diameter (Stage T1) and who underwent curative hepatectomy and long-term follow-up (range, 0.2 to 14.3 years). Patients were eligible for surgery if they had a tumor that met the diagnostic criteria for HCC and were in Child-Pugh class A (n = 59) or B (n = 11) status. Among the 70 patients, there was 1 operative death. Based on our typing system, the tumors were assigned as early HCC (n = 15), overt HCC (n = 52), and non-HCC tumor (n = 3). The rate of microscopic regional spread was lower in early HCCs than in overt HCCs (7% vs. 42%; P = .01). The early HCC group had a longer time to recurrence than did the overt HCC group (3.9 vs. 1.7 years; P < .001) and had no local recurrence. After a median follow-up of 6.3 years, both overall survival and recurrence-free survival in the early HCC group were significantly better than those in the overt HCC group (P = .01; P = .001). In these two groups, the 5-year rates of overall survival were 93% and 54% (P = .01), and those of recurrence-free survival were 47% and 16% (P = .05), respectively; a significant survival benefit persisted over a decade (57% vs. 21%; P = .05). The early HCC group was at a lower risk of recurrence (relative risk, 0.31; 95% CI, 0.15 to 0.65; P = .002) and death (relative risk, 0.26; 95% CI, 0.09 to 0.73; P = .01) than was the overt HCC group. Early HCC is a distinct clinical entity with a high rate of surgical cure, thereby justifying its definition. It can be a lesion that corresponds to "Stage 0" cancer in other organs.

Carcinoma, Hepatocellular↗

Dynamics of human cardiorespiratory responses to standing on one leg with eyes closed.

The postural control system has been extensively studied in terms of somatic motor function but little is known about its connection with human autonomic function. The purpose of this study was to determine the cardiorespiratory changes in response to the 1-min balance test that was performed by standing on one leg with eyes closed (SOLEC) or eyes open (SOLEO) in 12 healthy young women [mean age 20.7 (SD 3.3) years]. Heart rate (HR), respiratory rate (RR), duration of inspiration and expiration, tidal volume (VT), and oxygen uptake (VO2) were measured during the test. The SOLEC test produced rapid increases in HR at the onset. There were significant increases in HR later during the test (P < 0.05). Metabolic rate (VO2) showed a gradual increase during the SOLEC test, indicating that the late responses could have been partly due to metabolic changes. The RR increased significantly at the onset of the test (P < 0.05), and remained elevated until the end of the test. The early responses were considered to be mediated neurally through the postural control system which receives the afferent inputs arising from the vestibular system and from muscle proprioceptors of the leg. In contrast, SOLEO caused small insignificant changes in HR, RR, VT and VO2, suggesting that a visual input is essential for balancing a postural change. The SOLEC test may have potential as a test of autonomic function.

Adolescent↗

Molecular cloning of the chromosomal breakpoint in the LIS1 gene of a patient with isolated lissencephaly and balanced t(8;17).

Karyotypic analysis of a patient exhibiting a phenotype of isolated lissencephaly, and of her parents, revealed a de novo balanced translocation, t(8;17)(p11.2; p13.3). Since the lissencephaly (LIS1) gene was known to be located on 17p13.3, we investigated whether the translocation might involve this gene. We performed Southern analysis using cosmid clones that contained genomic sequences corresponding to LIS1, and found that the breakpoint was located within intron 1. As sequence analysis of the parental chromosomes in the vicinity of the breakpoint identified no additional putative transcripts, haploinsufficiency of the LIS1 gene is likely to be solely responsible for the patient's lissencephaly. Characterization of both breakpoints indicated a possible involvement of repetitive sequences in the recombigenic process that led to the translocation.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Alteration of the LIS1 gene in Japanese patients with isolated lissencephaly sequence or Miller-Dieker syndrome.

LIS1 is a genetic entity that is responsible for lissencephaly. Previously we have reported isolated lissencephaly sequence (ILS) in a Japanese patient carrying a balanced chromosomal translocation that disrupted the LIS1 gene. We examined mutations of LIS1 in 12 additional Japanese patients, 8 of them with ILS and 4 with Miller-Dieker syndrome (MDS). Fluorescence in situ hybridization (FISH) analysis disclosed deletions of part of the LIS1 gene or of the chromosomal region surrounding it in three of the ILS cases and in three of the MDS cases. In one of the remaining five ILS cases, SSCP analysis and subsequent sequence analysis identified a 1-bp deletion in exon IV, which can be expected to result in premature termination of the gene product. Our results indicate that in Japan, as elsewhere, abnormality of the LIS1 gene is a common cause of MDS/ILS.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Cardioprotective effect of succinate against ischemia/reperfusion injury.

We investigated the protective effects of succinate, which is a respiratory substrate and a potential antioxidant, on myocardial ischemia/reperfusion injury with the whole heart. Isolated rat hearts were loaded with 25-min normothermic global ischemia followed by 30-min reperfusion in a working heart model. Succinate administered either before reperfusion or added to the cardioplegic solution improved the postischemic cardiac function significantly. The hearts arrested with succinate-supplemented cardioplegic solution replenished high-energy phosphates and maintained the total adenine nucleotides during the reperfusion period, whereas those arrested with succinate-nonsupplemented cardioplegic solution replenished the high-energy phosphates less, and also lost total adenine nucleotides during that period. We thus conclude that succinate administered before reperfusion may decrease the degree of mitochondrial damage during reperfusion and thereby reduce the amount of myocardial ischemia/reperfusion injury.

Animals↗

Partial purification and characterization of sphingosine N-acyltransferase (ceramide synthase) from bovine liver mitochondrion-rich fraction.

Sphingosine N-acyltransferase (ceramide synthase, E.C. 2.3.1.24) was solubilized from bovine liver mitochondrion-rich fraction with n-octyl beta-D-thioglucoside as the detergent and partially purified by sequential chromatography on columns of DE-32, shingosine affinity, and Sepharose CL-6B. The partially purified preparation migrated on SDS-polyacrylamide gel electrophoresis as two major protein bands of 62 and 72 kDa. The molecular mass of the enzyme estimated by gel filtration was 240-260 kDa, suggesting that the partially purified enzyme is present in a subunit form or simply has an aggregative nature. The specific activity of the final preparation for the condensation of sphingosine with stearoyl-CoA increased by 98.7-fold compared with the starting material. The optimal pH value for the ceramide synthesis was 7.5. The partially purified enzyme had an apparent Km of 146 microM and a Vmax of 11.1 nmol/min/mg protein for stearoyl-CoA. The Km and Vmax values toward sphingosine were 171 microM and 11.3 nmol/min/mg protein, respectively. Interestingly, sphinganine was also a good substrate for this enzyme, and the Km and Vmax values were 144 microM and 8.5 nmol/min/mg protein, respectively.

Acyl Coenzyme A↗

Light and temperature cooperate to regulate the circadian locomotor rhythm of wild type and period mutants of Drosophila melanogaster.

In the wild type (Canton-S) and period mutant flies of Drosophila melanogaster, we examined the effects of light and temperature on the circadian locomotor rhythm. Under light dark cycles, the wild type and per(S) flies were diurnal at 25 degrees C. However, at 30 degrees C, the daytime activity commonly decreased to form a rather nocturnal pattern, and ultradian rhythms of a 2 approximately 4h period were observed more frequently than at 25 degrees C. The change in activity pattern was more clearly observed in per(0) flies, suggesting that these temperature dependent changes in activity pattern are mainly attributable to the system other than the circadian clock. In a 12h 30 degrees C:12h 25 degrees C temperature cycle (HTLT12:12), per(0) flies were active during the thermophase in constant darkness (DD) but during the cryophase in constant light (LL). The results of experiments with per(0);eya flies suggest that the compound eye is the main source of the photic information for this reversal. Wild type and per(0) flies were synchronized to HTLT12:12 both under LL and DD, while per(S) and per(L) flies were synchronized only in LL. This suggests that the circadian clock is entrainable to the temperature cycle, but the entrainability is reduced in the per(S) and per(L) flies to this particular thermoperiod length, and that temperature cycle forces the clock to move in LL, where the rhythm is believed to be stopped at constant temperature.

Journal Article↗