Biomedical subjects

S Takashima

Publications and source records attributed to S Takashima.

At least 217 records · Page 12Linked to original sources

PubMed1999

Detection of small peripheral lung cancer by digital chest radiography. Performance of unprocessed versus unsharp mask-processed images.

PURPOSE: To clarify whether processed digital chest radiography can improve the detection rate for small peripheral lung cancer. MATERIAL AND METHODS: Five radiologists independently interpreted 54 digitized chest radiographs of 18 patients with small peripheral lung cancers measuring less than 20 mm, which were displayed following 3 types of digital processing: 1) an original version; 2) unsharp mask processing with a type 1 filter (very low-frequency-enhancing, mid-frequency-suppressing, and high-frequency-enhancing filter); and 3) unsharp mask processing with a type 2 filter (very low- and high-frequency-enhancing filter). A total of 1,620 pooled observations were evaluated by receiver operating characteristic (ROC) analysis. RESULTS: The mean area under the ROC curves was 0.68 for the type 1 filter, 0.68 for the type 2 filter, and 0.65 for the unprocessed (original) image. There were no statistically significant differences among these 3 kinds of image processing (p>0.05). In all types of images, the small lung cancer with an alveolar lining tumor growth was less visible than a solid tumor growth (p<0.01); the sensitivity increased with tumor size when the 3 groups of cancers, those measuring less than 10 mm, 11-15 mm, and 16-20 mm, were compared (p<0.01). CONCLUSION: Unsharp mask-image processing of digital chest radiography will not improve the detection rate of small peripheral lung cancer, probably due to a substantial drawback: the limited conspicuity of cancer lesions in the surrounding lung and superposition of structures.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed1999

[Mechanism and possible biochemical modulation of capecitabine (Xeloda), a newly generated oral fluoropyrimidine].

A new 5-FU analog, Capecitabine (Xeloda; N-[1-(5-deoxy-b-D-ribofuranosyl)-5-fluoro-1, 2-dihydro-2-oxo-4-pyrimidyl]-n-penyl carbamate), was generated to decrease the incidence of GI toxicity and to increase the efficacy. Capecitabine is designed as a prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR), which is clinically used for gastric, breast and colorectal cancer patients undergoing single or combination chemotherapy in Japan. Capecitabine was converted to 5'-DFUR by either human carboxyestelase or cytidine deaminase, which were mainly localized in human liver. 5'-DFUR was converted to the active form of 5-FU by thymidine phosphorylase (dThdPase) in human tumors. The expression of dThdPase was higher in malignant tumors than in noninvolved normal tissues. In this regard, a high concentration of either 5'-DFUR or 5-FU in malignant tumors may be obtained by oral administration of Capecitabine. In addition, in vivo study showed synergistic or additive effects of Capecitabine combined with anti-cancer agents (Taxanes, Mitomycin C or Cyclophosphamide), cytokines, growth factors and hormonal agents. Capecitabine may be biochemically modulated by those agents in vivo. In the results of an early phase II study on breast cancer patients in Japan, a high efficacy rate and low toxicity were observed. Also, Capecitabine was already registered as 2nd- or 3rd-line treatments for breast cancer patients by the Food & Drug Administration of the USA. Capecitabine is one of the most promising orally administered 5-FU analogs.

Administration, Oral↗

PubMed1999

[Child neurology and neuronal apoptosis: introductory remarks].

Apoptosis is one type of cell death characterized morphologically by nuclear condensation and shrinkage of cell bodies. Thus, it is completely different from necrosis in features. Recently, it is suggested that apoptosis occurs in some neurodegenerative diseases of childhood as well as adulthood. Therefore, it is very important to reveal mechanisms of neuronal apoptosis. To the end, it is expected that new therapies will be developed to prevent the progress of neurodegenerative diseases. Based on such expectation, this symposium was organized to present recent progress in neuronal apoptosis research.

Apoptosis↗

PubMed1999

[Means of effective and practical intra-arterial chemotherapy for locally invasive bladder cancer--with special reference to clinical analysis of bladder cancer patients treated by intermittent intra-arterial infusion using an implantable port system].

Fifty-six patients with locally invasive bladder cancer were treated by chemotherapy with intermittent arterial infusion from an implanted reservoir and alteration of intrapelvic blood flow. The tip of an infusion catheter was inserted selectively into an internal iliac artery by an angiographic technique. Superior gluteal artery and the other internal iliac artery were then embolized with steel coils so that the drugs would perfuse throughout the tumor through a single catheter. Treatment consisted of intermittent injection of cisplatin (10 mg/body) and doxorubicin (10 mg/body) or epirubicin (10 mg/body) or pirarubicin (10 mg/body) in a ten-minute period every week (for the first 8 weeks) or every two weeks (after the 8th week). Fifty patients were objectively evaluated and the response rate was 80%. The overall survival rate in 54 patients at 1, 3, 5 and 8 years was 83.7%, 61.2%, 52.6%, and 52.6%. The 1-, 2-, 3-, 5- and 7-year disease free survival rate in evaluable 22 patients who showed a complete response (CR) was 91.8%, 85.2%, 65.6%, 58.3% and 58.3%. No serious side effects, such as severe myelosuppression or renal and/or liver dysfunction, were noted during treatment. These findings suggest that intermittent arterial chemotherapy with an implanted reservoir is clinically useful. This procedure appears safe and is easily performed in the outpatient clinic for the treatment of locally advanced bladder cancer.

Adult↗

PubMed1999

[Usefulness of low dose 5'-DFUR (5'-deoxy-5-fluorouridine) for advanced or recurrent breast cancer].

The usefulness of low dose (600 mg/day) 5'-DFUR for advanced or recurrent breast cancer was evaluated. Eight patients out of 38 showed a partial response (response rate 21.1%), 22 patients had no change, and 8 patients had progressive disease. The response rate was 31.0% in soft tissue and 9.1% in bone, both of which were slight. In both one-shot (200 mg) and continuous (1-4 months) administration of 5'-DFUR (600 mg/day), the concentration of 5'-DFUR of 5-FU in sera reached a plateau from 30 minutes to 2 hours after administration of 5'-DFUR, and disappeared after 3 hours. There were no significant differences in the concentration of 5'-DFUR of 5-FU in sera between one-shot and continuous administration. It is concluded that there was no accumulation of the drug after continuous administration of 5'-DFUR, and that low dose 5'-DFUR is a useful therapy for advanced or recurrent breast cancer.

Administration, Oral↗

PubMed1999

[Disappearance of globus pallidus hyperintensity in a patient with portal-systemic encephalopathy after occlusion of the shunt vessel].

A 67-year-old woman was admitted to our hospital with confusion and asterixis on January 23, 1994. She had had the same symptoms repeatedly. On admission she was disorientated, and had slurred speech and asterixis. Laboratory data showed hyperammonemia (84 micrograms/dl) with a poor ICG hepatic clearance (ICG15min = 32%), although hepatic failure did not exist. Abdominal ultrasonography, CT scan and liver biopsy showed no evidence of cirrhosis. Celiac arteriography revealed a large shunt vessel connecting the portal vein to the left renal vein. A 1.5 T magnetic resonance imaging (MRI) demonstrated a bilateral and symmetrical hyperintensity of the globus pallidus in the T1-weighted images. Portal-systemic encephalopathy recurred repeatedly in spite of the conservative therapy, and there was no evidence of the portal hypertension. Therefore, the operative procedure of ligation of the shunt vessel was done on February 21, 1995. After the operation, blood ammonia level and ICG hepatic clearance were normalized. She became free from encephalopathy. Twenty-seven months after the operation, the hyperintensity of the globus pallidus in the T1-weighted images completely disappeared. There have been several reports describing that the globus pallidus alterations on the T1-weighted images in patients with liver cirrhosis, manganese intoxication and portal-systemic encephalopathy. To our knowledge, this is the first case that the hyperintense signal of the basal ganglia in a patient with portal-systemic encephalopathy disappeared completely after occlusion of the shunt vessel.

Aged↗

PubMed1999

Developmental genetics of the Drosophila gut: specification of primordia, subdivision and overt-differentiation.

The Drosophila gut is composed of three major parts, the foregut, midgut and hindgut, which arise from anterior and posterior invaginations of the early blastoderm. We review the process of the specification of the gut primordia, subsequent subdivision and region-specific cell differentiation in terms of developmental genetics. Graded activities of maternal signals at anterior and posterior terminal domains of the blastoderm, being mediated by activities of two zygotic gap genes, tailless and huckebein, lead to the activation of key genes that determine the gut primordia: serpent (GATA factor gene) for the endodermal midgut; brachyenteron (Brachyury homolog) for the ectodermal hindgut. fork head (HNF-3 homolog) and caudal (Cdx homolog) are also essential for the development of all gut primordia or hindgut primordium, respectively. Subdivision of the midgut epithelium is regulated by inductive signals emanating from the visceral mesoderm, which is under the control of HOM-C genes. In contrast, pattern formation of the ectodermal foregut and hindgut is regulated by secreted signaling molecules, such as Wingless (Wnt homolog), Hedgehog and Decapentaplegic (Bmp-4 homolog), as in the case of segmented structures and imaginal discs. Finally, the gut is subdivided into at least 36 compartments that are recognized asminimum tissue units of regional differentiation. A few genes that are responsible for determining and maintaining the state of overt-differentiation of the compartments have also been reported. A marked feature of the genetic mechanism of the gut development is the unexpectedly wide spectrum of the similarities of relevant genes and regulatory pathways of gene expression between Drosophila and vertebrates, which may imply a prototypic style of body plan common to protostomes and deuterostomes.

Animals↗

PubMed1999

In vitro high resolution proton magnetic resonance study of human cerebellar development during the period from the fetus to childhood.

In the development of the human cerebellum, the intracellular metabolites were monitored during the period from the fetus to childhood by in vitro high resolution proton (1H) magnetic resonance (MR) spectroscopy. The spectra from fetus (15-30 post-menstrual weeks; n = 3), infant (1-24 months of age; n = 6) and child (7-14 years of age; n = 5) groups showed resonances from seventeen different metabolites. The level of N-acetylaspartate (NAA), one of the metabolites, was observed in age-dependent increases, two- and three-fold increases for infant and child groups from the NAA of the fetus group, respectively. The rapid increases in the creatine (Cre) level (approximately three-fold) in the fetus and infant groups were observed in the child group (approximately four-fold). Taurine (Tau) was noted at the highest concentration in the fetus group. Slight increases in concentrations of alanine, glutamate, glutamine, and glycine and a significant increase in the concentration of N-acetylaspartylglutamate were also noted in the fetus and infant groups. Other metabolite concentrations did not change significantly throughout the studied age groups. These findings indicate that synthesis of metabolites, especially of NAA and Cre, during the development of the cerebellum are closely correlated with mitochondrial energy metabolism, and as such, may reflect mitochondrial integrity in the cerebellum.

Aging↗

PubMed1998

Molecular cloning and functional expression of a fifth-type alpha 2,3-sialyltransferase (mST3Gal V: GM3 synthase).

The cDNA encoding a new type of alpha 2,3-sialyltransferase (mST3Gal V) was cloned from mouse brain cDNA library by PCR-based cloning approach using a pair of degenerate primers deduced from the nucleotide sequence information of mouse ST3Gal III and IV. The predicted amino acid sequence of mST3Gal V showed 27.3% and 26.4% identity to mST3Gal III and IV, respectively. The recombinant soluble mST3Gal V fused with protein-A, which expressed in the culture media of COS-7 cells, showed activity toward lactosylceramide (LacCer), and synthesized GM3. The apparent Km value for LacCer was 9.3 microM. mST3Gal V did not exhibit any activity toward other substrates we tested in this study, including glycolipids, glycoproteins and disaccharides. The mST3Gal V cDNA transfected F28-7 cells, which express large amount of lactosylceramide and very small amount of GM3 at native stage, expressed a large amount of GM3. The ST3Gal V gene was strongly expressed in mouse brain and liver, which contained a large amount of ganglioside. The gene expression seemed to be coincident with ganglioside expression in mouse. Thus, we conclude that mST3Gal V is the fifth-type alpha 2,3-sialyltransferase carrying GM3 synthetic activity.

Amino Acid Sequence↗

PubMed1998

The expression of late infantile neuronal ceroid lipofuscinosis (CLN2) gene product in human brains.

We raised polyclonal antibodies against a gene product responsible for late infantile neuronal ceroid lipofuscinosis (CLN2). By Western blotting, all three antisera recognized the CLN2 protein at approximately 49 kDa in human brain homogenates. Immunohistochemistry using the antisera demonstrated the granular labelling in the cytoplasm of cerebral neurons and glial cells. The immunoreactivity on Western blots was absent from the brain of a patient with CLN2. Our results suggest the usefulness of these antibodies for the diagnosis of CLN2, which currently requires demonstration of characteristic ultrastructure by electron microscopy.

Adolescent↗

PubMed1998

Overproduction of recombinant Trichoderma reesei cellulases by Aspergillus oryzae and their enzymatic properties.

We have established an expression system of Trichoderma reesei cellulase genes using Aspergillus oryzae as a host. In this system, the expression of T. reesei cellulase genes were regulated under the control of A. oryzae Taka-amylase promoter and the cellulase genes were highly expressed when maltose was used as a main carbon source for inducer. The production of recombinant cellulases by A. oryzae transformants reached a maximum after 3-4 days of cultivation. In some cases, proteolysis of recombinant cellulases was observed in the late stage of cultivation. The recombinant cellulases were purified and characterized. The apparent molecular weights of recombinant cellulases were more or less larger than those of native enzymes. The optimal temperatures and pHs of recombinant cellulases were 50-70 degrees C and 4-5, respectively. Among the recombinant cellulases, endoglucanase I showed broad substrate specificities and high activity when compared with the other cellulases investigated here.

Aspergillus oryzae↗

PubMed1998

Developmental characteristics of neuronal nitric oxide synthase (nNOS) immunoreactive neurons in fetal to adolescent human brains.

The developmental characteristics of the neuronal nitric oxide synthase (nNOS) immunoreactive neurons in the human brain were studied. In the frontal lobe, nNOS immunoreactive cells appeared as early as 18 gestational weeks (GW) in the subcortical plate and then increased predominantly in the subcortical white matter during the fetal period, while weakly immunoreactive neurons were found in the cortical II-IV layers after 26 GW. In the basal ganglia, immunoreactive neurons could be detected in the striatum as early as 13 GW, and then showed a transient increase with peaks at 23-24 GW and 33-36 GW in the putamen and caudate nucleus, respectively. In the cerebellum, immunoreactivity was detected in the Purkinje and basket cells after 23 GW and 31 GW, respectively. The immunoreactivity of internal granule cells was constantly weak. In the brain stem, constant and intense immunoreactive neurons were found in the central gray, pedunculopontine tegmental nucleus, solitary tract nucleus, and lateral reticular nucleus. The immunoreactivity in the neurons of the pontine nucleus and inferior olivary nucleus was transiently increased, with peaks at 38-40 GW and 23-24 GW, respectively. This characteristic nNOS development suggests that transient nNOS hyperproduction may contribute to neuron maturation as well as vulnerability in each period and region, and NO may play an important role in the basic development of human brain functions.

Adolescent↗

PubMed1998

Expression of the ataxia-telangiectasia gene (ATM) product in human cerebellar neurons during development.

Ataxia-telangiectasia (A-T) is a hereditary disorder, exhibiting progressive cerebellar ataxia. We investigated the expression of the ATM protein in the human CNS. By western blotting, the ATM protein was detected in the cerebellar cortex, but not in the cerebral cortex, at the late gestational stage. Immunohistochemistry revealed that cerebellar neurons, particularly Purkinje cells, were markedly immunoreactive during late prenatal and early postnatal periods, followed by persistent and moderate reactivity in Purkinje cells. The ATM protein was distributed within the cytoplasm of Purkinje cells, but not within the nuclei. The ATM protein seems to play a role as a cytoplasmic protein in neurons of the cerebellar cortex.

Adolescent↗

PubMed1998

Breast-Concerving Surgery Following Preoperative Radiotherapy to the Primary Breast Cancer of 3 cm or Larger: Histological Analysis of Size Reduction of the Tumors by Radiotherapy.

Fifteen women with primary breast cancer of 3 cm or larger were treated by radiotherapy of 5000 or 5100 cGy preoperatively for breast conservation. Among them, three responded completely to radiotherapy clinically, 6 did partially, and 6 showed minor response. Breast-concerving surgery was performed in all cases. Histologically one patient did not have cancer cells at surgery, while eight showed good response but had residual tumor, and the rest responded moderately. The histological margins were positive in six cases, of those three were positive due to an invasive component. Calculation of the size reduction of the primary tumor by radiotherapy at a histological level revealed that the invasive area of the tumors was 79.5% on average. There was a tendency, among well responding patients, to show a large reduction in size. However, the tumor cells tended to remain in the peripheral areas of the originally invasive areas. In summary, preoperative radiotherapy made the size of the primary tumors smaller in the majority of the cases clinically but the actual histological size reduction was relatively small in general. We conclude that preoperative radiotherapy is effective to extend the indications of conservative treatment in patients with a large primary breast cancer. However, care is required when we treat patients with a very large primary breast cancer conservatively.

Journal Article↗

PubMed1998

Mass screening for lung cancer with mobile spiral computed tomography scanner.

BACKGROUND: The incidence of and mortality from lung cancer have increased steadily. Most lung cancers are not localised when first detected, but early detection is mandatory to improve prognosis. Since curable early cases are hard to visualise with conventional chest radiography, a new diagnostic means must be found. We assessed whether population-based mass screening with a spiral computed tomography scanner could contribute substantially to detection of smaller cancers, and decrease mortality. METHODS: In 1996, we screened in a mobile unit 5483 individuals from the general population of Matsumoto, Japan, aged between 40 years and 74 years who had undergone annual chest radiography (miniature fluorophotography) and cytological assessment of sputum. All participants had a low-dose X-ray spiral computed tomography (CT) scan of the thorax; 3967 also underwent miniature fluorophotography. We compared smokers and non-smokers. Further assessments were done for probably benign but suspicious lesions; suspicion of cancer; and indeterminate small nodules by chest radiography and conventional CT, with additional transbronchial biopsy when possible. Thoracotomy was recommended when it was strongly suspected that the patients had lung cancer. FINDINGS: 19 patients were diagnosed as having lung cancer--14 with suspicion of lung cancer, three with benign but suspicious lesions, and two with indeterminate small nodules. 18 cases were surgically confirmed, and one was clinically diagnosed. The mean size of lesions was 17 mm (range 6-47). In four of 19 patients, lung abnormality was seen on CT and miniature fluorophotography. The lung-cancer detection rate with CT was 0.48%, significantly higher than the 0.03-0.05% for standard mass assessments done previously in the same area. CT missed one case that was found solely on a sputum cytology examination. INTERPRETATION: Our results show that miniature fluorophotography or conventional chest radiography, which have been the main diagnostic techniques for lung cancer, showed few small cancers. CT was more accurate in mass screening for lung cancer and led to early detection and an accurate diagnosis of lung cancer, and should be considered in future health plans.

Adult↗

PubMed1998

A developmental study of the dopamine D2R receptors in the human basal ganglia and thalamus.

The development of the dopamine D2R receptors (D2R) in the human basal ganglia (BG) and thalamus was investigated in 25 normal brains by means of an immunohistochemical method and Western blotting. Immunoreactivity to D2R was detected in the cytoplasm and dendrites of small and large neurons in the BG and thalamus. D2R-positive neurons were clearly observed at 19 weeks of gestation (GW) in the globus pallidus and thalamus, and at 21 GW in the striatum. The number of D2R-positive neurons gradually increased and reached a peak at 27 GW in the globus pallidus, at 39 GW in the thalamus, and at 1 month of age in the striatum. The number of D2R-positive large neurons in the globus pallidus and small neurons in the striatum decreased after 1 year and about 10 years of age, respectively. Western blotting confirmed the specificity of the immunohistochemistry. Our results suggest that the D2R protein begins to be synthesized at an early fetal stage in the BG and thalamus, and the development of D2R is mostly consistent with neuronal maturation in the BG. D2R may play an important role in regulating the neuronal development of the BG. The decrease in D2R-positive neurons may be related to D2R post-transcriptional regulation.

Adolescent↗

PubMed1998

Genomic structure and promoter activity of the mouse polysialic acid synthase (mST8Sia IV/PST) gene.

The mouse gene encoding ST8Sia IV/PST, one of two polysialic acid synthases, was isolated and characterized. The mST8Sia IV/PST gene was found to comprise over 60 kilobases and to be composed of five exons. Primer extension analysis revealed that transcription started from 333 nucleotides upstream of the translational initiation site. Transfection with nested deletion mutants of the 5'-flanking region fused to the luciferase reporter gene revealed that the promoter activity of the -107/+145 region was correlated with the gene expression of mST8Sia IV/PST in embryonal carcinoma P19 and neuroblastoma F11 cells. This proximal promoter region lacks an apparent TATA box but has putative binding sites for transcription factors Sp1 and NF-Y (CCAAT binding protein) at nucleotide positions -66/-57 and -47/-37, respectively. Individual deletions and mutations of the inverted Sp1 binding site or inverted NF-Y binding site caused significant reduction of the promoter activity, indicating that each binding site was involved in essential transcription control. Mobility shift assaying also revealed that Sp1 and NF-Y in a nuclear extract of P19 cells bind to the promoter region of the mST8Sia IV/PST gene. Deletion of the region from -60 to -40, which contains parts of both the Sp1 and NF-Y binding sites, completely abolished the promoter activity, suggesting that both Sp1 and NF-Y are synergetically involved in transcription regulation of the mST8Sia IV/PST gene in P19 and F11 cells. Although the overall structures of the two polysialic acid synthase genes (ST8Sia II/STX and IV/PST) are very similar, there is no extensive sequence homology between the 5'-flanking regions of the ST8Sia II/STX and IV/PST genes, suggesting that these two genes are expressed under different regulatory systems.

Animals↗

PubMed1998

Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, binds to two receptor tyrosine kinases, KDR/Flk-1 and Flt-1. We now describe the purification and the expression cloning from tumor cells of a third VEGF receptor, one that binds VEGF165 but not VEGF121. This isoform-specific VEGF receptor (VEGF165R) is identical to human neuropilin-1, a receptor for the collapsin/semaphorin family that mediates neuronal cell guidance. When coexpressed in cells with KDR, neuropilin-1 enhances the binding of VEGF165 to KDR and VEGF165-mediated chemotaxis. Conversely, inhibition of VEGF165 binding to neuropilin-1 inhibits its binding to KDR and its mitogenic activity for endothelial cells. We propose that neuropilin-1 is a novel VEGF receptor that modulates VEGF binding to KDR and subsequent bioactivity and therefore may regulate VEGF-induced angiogenesis.

Antigens, Surface↗