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Biomedical subjects

K Shimada

Publications and source records attributed to K Shimada.

At least 397 records · Page 22Linked to original sources

Nonnatural Branched Polysaccharides: Synthesis and Properties of Chitin and Chitosan Having alpha-Mannoside Branches.

Regioselective introduction of alpha-mannoside branches at C-6 of chitin and chitosan has been accomplished by a series of regioselective modification reactions starting from N-phthaloyl-chitosan as a key precursor. Glycosylation of the derived acceptor with reactive groups only at C-6 with an ortho ester of d-mannose proceeded smoothly in dichloromethane in the presence of trimethylsilyl trifluoromethanesulfonate, and the degree of branching was up to 0.6. Full deprotection gave chitosans with alpha-mannoside branches, which were subsequently transformed into the corresponding branched chitins by N-acetylation. The resulting branched polysaccharides showed a remarkable solubility in neutral water in sharp contrast to the insoluble linear chitin and chitosan. Concanavalin A exhibited a specific affinity for these products, which was ascribable to the presence of alpha-mannoside groups. Though nonnatural, the branched chitins were susceptible to lysozyme, and the enzymatic degradation was heavily dependent on the extent of branching. Furthermore, the branched chitosan exhibited considerable antimicrobial activity.

Journal Article↗

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↗

RAE28, BMI1, and M33 are members of heterogeneous multimeric mammalian Polycomb group complexes.

The Polycomb group loci in Drosophila encode chromatin proteins required for repression of homeotic loci in embryonic development. We show that mouse Polycomb group homologues, RAE28, BMI1 and M33, have overlapping but not identical expression patterns during embryogenesis and in adult tissues. These three proteins coimmunoprecipitate from embryonic nuclear extracts. Gel filtration analysis of embryonic extracts indicates that RAE28, BMI1 and M33 exist in large multimeric complexes. M33 and RAE28 coimmunoprecipitate and copurify as members of large complexes from F9 cells, which express BMI1 at very low levels, suggesting that different Polycomb group complexes can form in different cells. RAE28, BMI1 and M33 interact homotypically, and both RAE28 and M33 interact with BMI1, but not with each other. The domains required for interaction were localized. Together, these studies indicate that murine Polycomb group proteins are developmentally regulated and function as members of multiple, heterogeneous complexes.

Animals↗

MyoD is indispensable for muscle-specific alternative splicing in mouse mitochondrial ATP synthase gamma-subunit pre-mRNA.

Muscle-specific alternative RNA splicing is an essential step during myogenesis. In this paper, we report that a muscle-specific transcription factor, MyoD, plays a central role in the induction of muscle-specific alternative splicing during myogenesis. Recently, we reported that muscle and nonmuscle isoforms of the mitochondrial ATP synthase gamma-subunit (F1gamma) were generated by alternative splicing and that acidic stimulation promoted this muscle-specific alternative splicing (Endo, H., Matsuda, C., and Kagawa, Y. (1994) J. Biol. Chem. 269, 12488-12493). In this report, mouse myoblasts are shown to express the muscle-specific isoform of F1gamma after induction with low-serum medium (differentiation medium) or acidic medium, although myotube formation was not detected after acidic induction. RNA blot analysis revealed that the expression levels of both MEF2 and myogenin were increased by low-serum induction, but not by acidic induction. High expression of MyoD mRNA was observed after both types of induction. Overexpression of exogenous MyoD in fibroblasts showed that MyoD was necessary for muscle-specific alternative splicing in both types of induction. Exogenous Id, a negative regulator of MyoD, blocked muscle-specific alternative splicing of F1gamma pre-mRNA by both types of induction. In addition, MyoD induced several muscle-specific alternative splicings, including structural protein pre-mRNAs such as beta-tropomyosin and neural-cell adhesion molecule and transcriptional protein pre-mRNAs such as MEF2A and MEF2D. Our analysis of the two induction systems shows a common MyoD-dependent mechanism of muscle-specific alternative splicing in several genes, independent of MEF2 and myogenin.

Adenosine Triphosphatases↗

Left ventricular function and coagulation activity in healed myocardial infarction.

We investigated the plasma levels of molecular markers for the thrombotic and fibrinolytic status in patients with healed myocardial infarction to determine the relation between left ventricular (LV) function and coagulation activity. Our findings demonstrated that the coagulation activity was increased in patients with healed myocardial infarction along with LV dysfunction, suggesting that anticoagulant therapy is considered in patients with severe LV dysfunction to prevent systemic thromboembolism.

Blood Coagulation Factors↗

Staggered movement of an actin filament sliding on myosin molecules in the presence of ATP.

An actin filament sliding on myosin molecules in the presence of an extremely low concentration of ATP exhibited a staggered movement. Longitudinally sliding movement of the filament was frequently interrupted by its non-sliding, fluctuating movements both in the longitudinal and transversal directions. Intermittent sliding movements of an actin filament indicate establishment of a coordination of ATP-mediated active sites distributed along the filament.

Actins↗

Tec and Jak2 kinases cooperate to mediate cytokine-driven activation of c-fos transcription.

Although transcriptional activation of the c-fos proto-oncogene plays an intrinsic role in the mechanism of blood cell growth, it is still obscure how protein-tyrosine kinases (PTKs) regulate the cytokine-driven c-fos activation pathway. We present here that Tec PTK is tyrosine-phosphorylated and activated by granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation in a human GM-CSF-dependent cell line. Moreover, we could show that introduction of Tec into mouse BA/F3-hGMRalphabeta cells can profoundly activate the c-fos promoter in response to GM-CSF or to interleukin-3 (IL-3). In contrast, introduction of a kinase-deleted Tec could suppress cytokine-driven c-fos activation, indicating that Tec is directly involved in the regulation of c-fos transcription. Interestingly, strong activation by Tec of the c-fos promoter was blocked by the co-expression of dominant negative Jak2. The molecular interaction between Tec and Jak2 was then investigated both in mammalian and insect cell systems, revealing that they can not only bind to each other, but either of the two can phosphorylate the other. Thus, Tec and Jak2 can "cross-talk" in a complexed way to mediate cytokine-driven c-fos activation.

Amino Acid Sequence↗

Role of left ventricular mass/volume ratio on transmitral flow velocity patterns from infancy to childhood.

Age-related changes in left ventricular diastolic filling have been reported to occur in normal children in studies using Doppler echocardiographic methods. However, little information currently exists on the relationships between transmitral flow velocity patterns and the left ventricular mass. We measured left ventricular end-diastolic volume, left ventricular mass, mass/volume ratio, and transmitral flow velocity patterns by M-mode and Doppler echocardiography in 165 normal children aged 5 days to 195 months. Subjects were divided into 6 age groups: <1; 1 to <3; 3 to <5; 5 to <7; 7 to <9; and > or = 9 years old. The left ventricular end-diastolic volume and mass increased progressively with increasing age. However, the mass/volume ratio in infants <1 year was significantly higher than that in infants 1 to <3 years (1.32+/-0.25 vs. 1.14+/-0.16, p<0.01) without any changes of the ratio thereafter. The peak E wave in infants <1 year was significantly lower than that in 1 to <3 years (71+/-18 vs. 92+/-13 cm/s, p<0.01) without changes thereafter. As the flow velocity time integral of E wave increased and that of A wave remained constant, the flow velocity time integral of E/A wave increased with increasing age. The early diastolic tilling fraction in infants <1 year was lower than that in infants 1 to 3 years. (0.61+/-0.07 vs. 0.70+/-0.06, p<0.01). The atrial filling fraction in infants <1 year was higher than that in infants 1 to <3 years (0.40+/-0.08 vs. 0.30+/-0.06, p<0.01) with a little decrease thereafter. The peak E wave, early diastolic tilling fraction, and the atrial filling fraction correlated with the logarithm of age (p<0.01). Age-related changes in these Doppler echocardiographic findings suggest reduced left ventricular early diastolic filling patterns. The mass/volume ratio correlated linearly with peak E wave, early diastolic filling fraction, and atrial filling fraction (r=-0.38, -0.33, and 0.26, p<0.01). No significant relationships between mass/volume ratio and the other Doppler indices were found. Thus, the age-related reduction in the mass/volume ratio may be one of the mechanisms underlying age-related changes in the early diastolic ventricular filling as assessed by Doppler echocardiography.

Aging↗

Identification of sperm-bearing female-specific chromosome in the sex-reversed chicken.

Sexual differentiation in the female chick embryo was phenotypically reversed to the male sex by injection of an aromatase inhibitor (Fadrozole, 0.1 mg/egg) into the embryo at day 5 of incubation. The birds were raised to 10 months of age, and the morphology of the gonads of sex-reversed hens were examined by the light-microscopic morphology, and the presence of the W chromosome gene was determined by fluorescence in situ hybridization (FISH) technique and used for PCR analysis of a single isolated sperm. The sex-reversed hens possessed two testes with a fully developed oviduct on the left side. The testes contained essentially the same cellular components as those of normal testes, although sperm counts were low. FISH analysis revealed numerous spermatids and several sperm bearing W-chromosomes, indicating that the second meiosis occurred normally but that the transformation from the spermatid to the spermatozoon is partially impaired. PCR analysis using the DNA of a single sperm also indicates that sperm-carrying the W chromosome were produced.

Animals↗

Effect of mitral regurgitation on coagulation activity in atrial fibrillation.

We measured the plasma levels of molecular markers for thrombotic and fibrinolytic status in patients with nonrheumatic atrial fibrillation (AF) to investigate the relation between coagulation activity and mitral regurgitation (MR). Our findings demonstrated that a greater degree of MR was associated with less coagulation activity in patients with nonrheumatic AF, suggesting that MR protects against left atrial thrombus and systemic thromboembolism.

Aged↗

Helical computed tomography in the diagnosis of portal vein invasion by pancreatic head carcinoma: usefulness for selecting surgical procedures and predicting the outcome.

OBJECTIVE: To evaluate the use of helical computed tomography (CT) in diagnosing portal vein (PV) invasion by pancreatic head carcinoma and its usefulness in predicting outcome. DESIGN: Validation cohort study. SETTING: Tertiary care public hospital. PATIENTS: Twenty-seven patients with carcinoma involving the pancreatic head were preoperatively studied with helical CT. All patients underwent resection. MAIN OUTCOME MEASURE: By quantifying the contact between the tumor and PV on helical CT, the relationship between them was classified into 1 of 4 types: type 1, visible fat layer between PV and the tumor; type 2, with the total PV circumference defined as 360 degrees, contact between the tumor and PV was considered to be 90 degrees or less; type 3, contact ranged between 91 degrees and 180 degrees; and type 4, contact greater than 180 degrees. Helical CT results were compared with intraoperative observation, histological findings of the resected specimen, and postoperative course. RESULTS: When helical CT showed type 3 or 4, the case was diagnosed as positive for PV invasion. Sensitivity, specificity, and overall accuracy were 83%, 100%, and 89% when compared with the intraoperative assessment, and 92%, 79%, and 85% with the histological assessment, respectively. One- and 2-year survival rates were 86% and 69% for type 1, 100% and 75% for type 2, and 33% and 12% for type 3, respectively. The survival rates of patients with types 1 and 2 were significantly higher than that of those with type 3 (P<.05). All 3 patients with type 4 died within 9 months. CONCLUSIONS: Helical CT facilitates detection of PV invasion by pancreatic head carcinoma. The extent of PV involvement reflected the outcome after pancreatectomy.

Adenocarcinoma↗

Small polypoid lesions of the gallbladder: differential diagnosis and surgical indications by helical computed tomography.

OBJECTIVES: To demonstrate the helical computed tomographic (CT) features of small polypoid lesions of the gallbladder and to establish a clinical strategy based on CT findings for the treatment of such lesions. DESIGN: Validation cohort study. SETTING: Tertiary care public hospital. PATIENTS: Thirty-one patients with polypoid lesions of the gallbladder (< or = 3 cm) underwent CT followed by resection. MAIN OUTCOME MEASURE: The detectability of the lesions on both unenhanced and enhanced CT and the configuration of the lesions on enhanced CT were prospectively evaluated in comparison with the histopathological findings. RESULTS: Unenhanced CT detected 14 (45%) of the 31 lesions, whereas enhanced CT detected all of the lesions. The detection rates of the neoplastic lesions (adenoma, adenocarcinoma, and metastatic tumor) and cholesterol polyps were 81% (13/16) and 7% (1/15), respectively (P<.001). Among the 20 lesions demonstrated as pedunculated, 6 (30%) were neoplastic, whereas 10 (91%) of the 11 lesions demonstrated as sessile were neoplastic (P<.001). When a lesion was demonstrated on unenhanced CT or its shape was sessile on enhanced CT, the case was diagnosed as a neoplastic lesion. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the CT diagnosis of the neoplastic lesions were 88% (14/16), 87% (13/15), 88% (14/16), 87% (13/15), and 87% (27/31), respectively. CONCLUSION: Computed tomography can differentiate neoplastic and nonneoplastic small polypoid lesions of the gallbladder and reliably identify the presence of neoplastic lesions that should be resected.

Adult↗

Efficacy and safety of early coronary stenting for unstable angina.

To determine the efficacy and safety of early coronary stenting for unstable angina, we studied 91 consecutive patients with unstable angina. Thirty-one patients underwent stenting 72 h or more after admission, and another 60 patients underwent stenting within 72 h of admission. The clinical and angiographic follow-up had been done for 6 mo. There were no differences between the baseline clinical and angiographic characteristics of both groups. The maximum balloon pressure was higher (14.1 +/- 1.2 vs. 12.6 +/- 0.9, P < 0.01) and the hospital stay was shorter (9.7 +/- 2.7 vs. 18.7 +/- 5.8 d, P < 0.0001) in the early stenting group. These two groups were similar in the clinical success rate (90.0% vs. 93.5%), without any abrupt closure, subacute thrombosis, death, myocardial infarction, or coronary bypass surgery. These findings indicate that early stenting can be useful in patients with unstable angina.

Aged↗

Monocyte-endothelial cell interaction in atherogenesis and thrombosis.

Cellular interactions between leukocytes and the endothelium are critical events in vascular biology, such as atherosclerosis and acute coronary syndrome. When monocytes and endothelial cells are activated via direct cell-cell interaction, both types of cells express several biologically active molecules such as adhesion molecules, cytokines, coagulation and fibrinolytic factors, metalloproteinases, and vasoactive substances. All of these molecules could contribute to atherogenesis and thrombosis.

Animals↗

Hypocalcemic heart failure: a reversible form of heart muscle disease.

This paper reports the case of a 53-year-old woman with hypocalcemia-induced reversible cardiomyopathy. Laboratory tests showed hypocalcemia caused by idiopathic hypoparathyroidism. Her left ventricular dysfunction persisted for a long period even after normalization of the serum calcium level. Observations suggest that physicians should be aware that hypocalcemia can be a reversible cause of cardiomyopathy and congestive heart failure.

Female↗

Inducible nitric oxide synthase and atherosclerosis.

Nitric oxide (NO) synthase induction in vascular smooth muscle cells may play a role in local vascular injury associated with atherosclerosis or postangioplasty restenosis by inhibiting smooth muscle cell proliferation and contraction, as well as by preventing leukocyte and platelet adhesion. The expression of inducible NO synthase is increased in balloon-injured arteries of experimental animals or in human atherosclerotic lesions. Replacement therapy with NO donors or NO synthase gene transfer may improve the clinical course of atherosclerosis or restenosis.

Animals↗