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S Tanda

Publications and source records attributed to S Tanda.

At least 19 recordsLinked to original sources
PubMed2006

Histological analysis on adhesive molecules of renal intravascular large B cell lymphoma treated with CHOP chemotherapy and rituximab.

A 48-year-old man was admitted to our hospital for investigation of mild renal dysfunction. A blood examination revealed mild elevation of creatinine level (1.77 mg/dl). Urinary examination revealed mild protein excretion (0.54 g/day) and microhematuria; renal biopsy revealed the focal proliferation of large mononuclear cells with mitosis in glomerular capillaries. According to immunohistochemical analysis, the intravascular lymphomatous cells stained positively with anti-leukocyte common antigen (LCA: CD45) and CD20, indicating a B lymphocyte lineage. In electron microscopy, the glomerular capillary was filled with lymphoma cells and epithelial foot process fusion was noted. Immunohistochemical analysis on adhesive molecules revealed a lack of CD11a expression on lymphoma cells, but positive CD54 expression on endothelial cells. Systemic 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal uptake of isotopes. On the basis of these findings, we diagnosed intravascular diffuse large B cell lymphoma localized in the kidney. Despite treatment with rituximab and CHOP (prednisolone, doxorubicin, vincristine, cyclophosphamide) for 3 cycles at 1-month intervals, the renal dysfunction did not change. In histopathological analysis of the second biopsy, lymphoma cells disappeared, but focal segmental glomerulosclerosis and moderate interstitial fibrosis were noted. Electron microscopic findings revealed severe subendothelial edema with mesangial interposition, indicating severe endothelial damage. Epithelial foot process fusion was improved. These pathological analyses let us conclude that a lack of CD11a could be a candidate factor for prevention of the extravasation of lymphoma cells from blood vessels in our patient. We also presumed that the intraglomerular endothelial damage occurred due to chemotherapy-associated cell injury.

Antibodies, Monoclonal↗
PubMed2001

Vascular morphogenesis and remodeling in a model of tissue repair: blood vessel formation and growth in the ovarian pedicle after ovariectomy.

To investigate mechanisms of vascular morphogenesis in tissue repair, we performed ovariectomy with resection of the corresponding branches of the ovarian vessels in nude mice. This induces a vascular network remodeling response in the healing ovarian pedicle. Reconstruction of 2000 histological serial sections demonstrated that a new vascular network composed of venous-venous loops forms in the wall of the dilated ovarian vein. Preexisting veins of all sizes, including a branch of the main artery, are subjected to segmentation. Loop formation and segmentation are based on intussusceptive microvascular growth. Loop formation is followed by elongation. Loop remodeling occurs also by intussusception and results in the formation of compound loop systems. All loop systems observed were completely patent. Blind-ending sprouts were extremely rare. Anastomoses between the preexisting vessels subjected to segmentation and the loop systems were established to include the newly formed vessels into the preexisting vascular network. The formation of an increasing number of patent loop systems likely decreases hypoxia and subsequently arrests angiogenesis with transformation of the granulation tissue into a scar. Loop formation also occurred inside a large thrombus that occluded a part of the lumen of the main vein.

Animals↗
PubMed2001

Vascular morphogenesis and remodeling in a human tumor xenograft: blood vessel formation and growth after ovariectomy and tumor implantation.

To determine mechanisms of blood vessel formation and growth in solid tumors, we used a model in which LS174T human colon adenocarcinomas are grown in the isolated ovarian pedicle of nude mice. Reconstruction of 3500 histological serial sections demonstrated that a new vascular network composed of venous-venous loops of varying sizes grows inside the tumor from the wall of the adjacent main vein. Loops elongate and remodel to establish complex loop systems. The mechanisms of loop formation and remodeling correspond to intussusceptive microvascular growth (IMG). In the tissue surrounding the tumor segmentation, another mechanism of IMG is prevalent in venous vessels. Comparison to vascular morphogenesis in the ovariectomized pedicle not only confirms the existence of corresponding mechanisms in both systems, but also reveals numerous sprouts that are superimposed onto loop systems and pathological deviations of loop formation, remodeling, and segmentation in the tumor. These pathological mechanisms interfere with vessel patency that likely cause heterogenous perfusion and hypoxia thus perpetuating angiogenesis. Blood vessel formation based on IMG was also detected in a large thrombus that completely occluded a part of an ovarian artery branch.

Adenocarcinoma↗
PubMed2001

The Drosophila UBC9 homologue lesswright mediates the disjunction of homologues in meiosis I.

BACKGROUND: In Saccharomyces cerevisiae and other organisms, the UBC9 (ubiquitin-conjugating 9) protein modifies the function of many different target proteins through covalent attachment of the ubiquitin-like protein SMT-3/SUMO. RESULTS: Using a second-site suppression screen of a mutation in the nod locus with a variable meiotic phenotype, we have identified mutations in the Drosophila melanogaster UBC9 homologue, encoded by the gene lesswright (lwr). lwr mutations dominantly suppress the nondisjunction and cytological defects of female meiotic mutations that affect spindle formation. The lwr lethal phenotype is rescued by a Drosophila UBC9/lwr transgene. CONCLUSIONS: We suggest that LWR mediates the dissociation of heterochromatic regions of homologues at the end of meiotic prophase I. Our model proposes that when there is less LWR protein, homologues remain together longer, allowing for more normal spindle formation in mutant backgrounds and therefore more accurate meiotic chromosome segregation.

Alleles↗
PubMed2000

Decreased binding sites of angiotensin II in rat LY-80 and AH109A tumour and human gastric cancer using quantitative in vitro autoradiography.

BACKGROUND: Under systemic hypertension induced by angiotensin II (AII) infusion, an attenuated vasoconstrictive response to the infusion in tumours was observed and a marked increase in tumour blood flow was observed in comparison with that in normal tissues. The results show a parallel circuit that connects the vascular bed of the pre-existing tissue to that of the tumour. The phenomenon was absent when hypertension was provoked by other vasoconstrictive agents such as norepinephrine or endothelin-1. However, the biological basis for this attenuated vasoconstrictive response to angiotensin II observed in tumours has not been fully elucidated. METHODS: We assessed this response to characterise the angiotensin II receptor density and affinity in normal and tumour tissues. AH109A and LY80 tumour cell lines were transplanted to the skin in nude rats. Four weeks later, the rats were sacrificed. 125I-[Sar1, Ile8] angiotensin II was used to map its receptors in rat tissues using in vitro computerised autoradiography. Operated human gastric cancer tissues from a 49-year-old and a 66-year-old male patients were also investigated. RESULTS: The numbers of angiotensin II receptors were markedly reduced in tumour tissues without a change of affinity. The numbers in AII-R in tumours were shown to be mainly AT1 by the marked reduction in radioligand binding achieved by losartan but not by PD123177. The same results were observed in human gastric cancer. CONCLUSIONS: These results suggest that the decrease in angiotensin II receptors in tumours may explain the haemodynamic effect of angiotensin II-induced hypertension on tumour blood flow. This condition for drug delivery to tumour tissue may play a major role in enhancing the therapeutic effects of chemotherapy.

Aged↗
PubMed2000

[Tumor microcirculation and selective enhancement of drug delivery--clinical applications based on pathophysiological experiments].

Tumor tissue is composed of cancer cells (parenchyma) and tumor vessels (interstitium). Many investigators have pointed out that blood flow in tumors has a very inhomogenous distribution, and that this inhomogeneity in blood flow increases as tumors grew. This would be a certain cause of insufficient drug delivery to tumor tissues. Among the experimental evidence using Yoshida Sarcoma and Ascites Hepatomas, functional differences in microcirculation between tumor and normal tissues were found by Suzuki et al. (1977). Under hypertensive state induced by the continuous infusion of angiotensin II, tumor blood flow increased remarkably, while there was no change or decrease in blood flow in normal tissues such as the brain, bone marrow, liver and kidney. Moreover, the increase in blood flow in tumors was selective, as the mean blood pressure remained at the level of 150 mmHg. Increases were confirmed not only in many growing sites such as in the liver, muscle, subcutis, and even microfoci, but also in various kinds of xenografted human tumors and autochthonous tumors. Augmentation of the anti-tumor effects of angiotensin II-induced hypertension chemotherapy (IHC) for advanced gastric carcinoma was revealed in two randomized controlled trials (RCT-1 & 2) of collaborative study groups in Japan. The response rates were 42.9% vs 10.5% in RCT-1 and 31.3% vs 6.7% in RCT-2. The frequencies of toxicities were not statistically different. In the results of phase II studies from 1978 to 1994 (OPN-1) and 1995 to 1999 (OPN-2) for advanced gastric carcinoma (GC), the response rates were 37.9% and 35.7%. Down staging in which the conclusive stage score was lower than the score of the clinical stage, was observed in 8 out of 94 cases (19%) with primary lesions in total and in 30 patients (63%) receiving reduction surgery after IHC, since 1978. It is very important for exact evaluation after chemotherapy to understand or estimate the pathohistological changes in the tumor and its degenerated or repaired tissues, which present various clinical images. In the present study, the actual administered dose intensity of adriamycin (aDIadm) was 5.9 +/- 2.4 mg/sqm/w, and the ratio of aDIadm to the proposed DIadm of reported FAM/FAP schedules was 0.78 +/- 0.32. IHC with smaller DI could lead to a reduction in the accumulation of toxicities of anti-cancer drugs in the host. In conclusion, IHC might be applied to all kinds of tumors to enhance the chemotherapeutic effects through selective increase of drug delivery to tumors.

Animals↗
PubMed1999

Molecular cloning of a putative cyclic nucleotide-gated ion channel cDNA from Limulus polyphemus.

Cyclic nucleotide-gated channels have been proposed to mediate the electrical response to light in the ventral photoreceptor cells of the horseshoe crab, Limulus polyphemus. However, a cyclic nucleotide-gated channel has not been identified from Limulus. We have cloned a putative full-length cyclic nucleotide-gated channel cDNA by screening cDNA libraries constructed from Limulus brain using a probe developed from Limulus ventral eye nerves. The putative full-length cDNA was derived from two overlapping partial cDNA clones. The open reading frame encodes 905 amino acids; the sequence shows 44% identity to that of the alpha subunit of the bovine rod cyclic GMP-gated channel over the region containing the transmembrane domains and the cyclic nucleotide binding domain. This Limulus channel has a novel C-terminal region of approximately 200 amino acids, containing three putative Src homology domain 3 binding motifs and a putative coiled-coil domain. The possibility that this cloned channel is the same as that detected previously in excised patches from the photoreceptive membrane of Limulus ventral photoreceptors is discussed in terms of its sequence and its expression in the ventral eye nerves.

Animals↗
PubMed1999

A highly conserved sequence in the 3'-untranslated region of the drosophila Adh gene plays a functional role in Adh expression.

Phylogenetic analysis identified a highly conserved eight-base sequence (AAGGCTGA) within the 3'-untranslated region (UTR) of the Drosophila alcohol dehydrogenase gene, Adh. To examine the functional significance of this conserved motif, we performed in vitro deletion mutagenesis on the D. melanogaster Adh gene followed by P-element-mediated germline transformation. Deletion of all or part of the eight-base sequence leads to a twofold increase in in vivo ADH enzymatic activity. The increase in activity is temporally and spatially general and is the result of an underlying increase in Adh transcript. These results indicate that the conserved 3'-UTR motif plays a functional role in the negative regulation of Adh gene expression. The evolutionary significance of our results may be understood in the context of the amino acid change that produces the ADH-F allele and also leads to a twofold increase in ADH activity. While there is compelling evidence that the amino acid replacement has been a target of positive selection, the conservation of the 3'-UTR sequence suggests that it is under strong purifying selection. The selective difference between these two sequence changes, which have similar effects on ADH activity, may be explained by different metabolic costs associated with the increase in activity.

Alcohol Dehydrogenase↗
PubMed1999

RNA secondary structure and compensatory evolution.

The classic concept of epistatic fitness interactions between genes has been extended to study interactions within gene regions, especially between nucleotides that are important in maintaining pre-mRNA/mRNA secondary structures. It is shown that the majority of linkage disequilibria found within the Drosophila Adh gene are likely to be caused by epistatic selection operating on RNA secondary structures. A recently proposed method of RNA secondary structure prediction based on DNA sequence comparisons is reviewed and applied to several types of RNAs, including tRNA, rRNA, and mRNA. The patterns of covariation in these RNAs are analyzed based on Kimura's compensatory evolution model. The results suggest that this model describes the substitution process in the pairing regions (helices) of RNA secondary structures well when the helices are evolutionarily conserved and thermodynamically stable, but fails in some other cases. Epistatic selection maintaining pre-mRNA/mRNA secondary structures is compared to weak selective forces that determine features such as base composition and synonymous codon usage. The relationships among these forces and their relative strengths are addressed. Finally, our mutagenesis experiments using the Drosophila Adh locus are reviewed. These experiments analyze long-range compensatory interactions between the 5' and 3' ends of Adh mRNA, the different constraints on secondary structures in introns and exons, and the possible role of secondary structures in RNA splicing.

Alcohol Dehydrogenase↗
PubMed1998

The Drosophila semushi mutation blocks nuclear import of bicoid during embryogenesis.

The maternal transcript of the anterior segmentation gene bicoid (bcd) is localized at the anterior pole of the Drosophila egg and translated to form a gradient in the nuclei of the syncytial blastoderm embryo after fertilization [1-3]. The nuclear gradient of Bcd protein - a transcription factor - leads to differential expression of zygotic segmentation genes. The rapid nuclear division during this stage [4] requires that Bcd quickly enters the nuclei after each mitosis using an active nuclear import system. Nuclear transport depends on the asymmetrical distribution of two forms of the small GTPase Ran: Ran-GTP is concentrated in the nucleus and Ran-GDP in the cytoplasm [5-8]. Ran requires RanGTPase-activating protein-1 (RanGAP1) on the cytoplasmic side of nuclear pore complexes to convert Ran-GTP to Ran-GDP. In vitro studies with vertebrate proteins demonstrate that the RanGAP1 associated with the nuclear pore complex is modified with small ubiquitin related modifier-1 (SUMO-1) by a ubiquitin-conjugating enzyme (E2 enzyme) [9-15]. Here, we show that mutation of the Drosophila semushi (semi) gene, which encodes an E2 enzyme, blocks nuclear import of Bcd during early embryogenesis and results in misregulation of the segmentation genes that are Bcd targets. Consequently, semi embryos have multiple defects in anterior segmentation. This study demonstrates that an E2 enzyme is required for nuclear transport during Drosophila embryogenesis.

Animals↗
PubMed1998

Long-range base pairing in Drosophila and human mRNA sequences.

The potential for long-range base pairing between the 5' and 3' ends of mRNA molecules was examined for 134 Drosophila and 204 human sequences collected from the GenBank database. Each sequence was divided into two parts, a 5' sequence taken from the start of the protein-encoding region and a 3' sequence taken from the end of the transcript. The strongest RNA pairing stem between each pair of 5' and 3' sequences was identified and scored using an alignment program modified to incorporate RNA base pairing. The observed pairing scores were then compared with a random distribution of scores generated by aligning each 5' sequence to random permutations of its corresponding 3' sequence. For both the Drosophila and the human mRNAs, the observed pairing scores were significantly biased toward the upper tail of the random distributions, with 61% of the Drosophila sequences and 64% of the human sequences falling within the upper half of the random distributions. This suggests that a pattern of long-range base pairing may be a common feature of eukaryotic mRNAs. We have also analyzed a subset of Drosophila and human mRNAs which show the greatest potential for long-range pairing. The human pairings appear to be stronger and localized to more specific regions near the ends of the mRNA sequence than those of Drosophila.

Animals↗
PubMed1998

Endothelin receptors and angiotensin II receptors in tumor tissue.

In cancer chemotherapy, selective enhancement of drug delivery to tumor tissue is essentially important for increase of chemotherapeutic effects. An attenuated vasoconstrictive response to angiotensin II (Ang II) in tumors and a marked increase in tumor blood flow were observed compared with normal tissues during systemic hypertension induced by Ang II infusion. The phenomenon was absent when hypertension was provoked by endothelin-1 (ET-1). We assessed this response to characterize ET receptor and Ang II receptor density and affinity in normal and tumor tissues. The tumor cell line LY80 was transplanted to the skin in nude rats. Four weeks later the rats were sacrificed. [125I] ET-1 and [125I Sar1, Ile8]-Ang II were used to map the receptors for ET and Ang II in rat tissues using computerized in vitro autoradiography. A moderately high density of ET receptors, (ETB > ETA) was found in tumors. The Ang II receptors were markedly reduced in tumor tissues without changes in the affinity. These results suggest that the decrease in Ang II receptors but not ET receptors in tumors may explain the hemodynamic effect of Ang II-induced hypertension and ET-induced hypertension on tumor blood flow.

Angiotensin II↗
PubMed1997

Site-directed mutations reveal long-range compensatory interactions in the Adh gene of Drosophila melanogaster.

Long-range interactions between the 5' and 3' ends of mRNA molecules have been suggested to play a role in the initiation of translation and the regulation of gene expression. To identify such interactions and to study their molecular evolution, we used phylogenetic analysis to generate a model of mRNA higher-order structure in the Adh transcript of Drosophila melanogaster. This model predicts long-range, tertiary contacts between a region of the protein-encoding sequence just downstream of the start codon and a conserved sequence in the 3' untranslated region (UTR). To further examine the proposed structure, site-directed mutations were generated in vitro in a cloned D. melanogaster Adh gene, and the mutant constructs were introduced into the Drosophila germ line through P-element mediated transformation. Transformants were spectrophotometrically assayed for alcohol dehydrogenase activity. Our results indicate that transformants containing a silent mutation near the start of the protein-encoding sequence show an approximately 15% reduction in alcohol dehydrogenase activity relative to wild-type transformants. This activity can be restored to wild-type levels by a second, compensatory mutation in the 3' UTR. These observations are consistent with a higher-order structure model that includes long-range interactions between the 5' and 3' ends of the Adh mRNA. However, our results do not fit the classical compensatory substitution model because the second mutation by itself (in the 3' UTR) did not show a measurable reduction in gene expression.

Alcohol Dehydrogenase↗
PubMed1997

oroshigane, a new segment polarity gene of Drosophila melanogaster, functions in hedgehog signal transduction.

Here we describe a new segment polarity gene of Drosophila melanogaster, oroshigane (oro). Identified as a dominant enhancer of Bar (B), oro is also recessive embryonic lethal, and homozygous oro embryos show variable substitution of naked cuticle with denticles. These patterns are distinctly similar to those of hedgehog (hh) and wingless (wg) embryos, which indicates that oro functions in determining embryonic segment polarity. Evidence that oro function is involved in Hh signal transduction during embryogenesis is provided by its genetic interactions with the segment polarity genes patched (ptc) and fused (fu). Furthermore, ptcIN is a dominant suppressor of the oro embryonic lethal phenotype, suggesting a close and dose-dependent relationship between oro and ptc in Hh signal transduction. oro function is also required in imaginal development. The oroI allele significantly reduces decapentaplegic (dpp), but not hh, expression in the eye imaginal disc. Furthermore, oro enhances the fui wing phenotype in a dominant manner. Based upon the interactions of oro with hh, ptc, and fu, we propose that the oro gene plays important roles in Hh signal transduction.

Animals↗
PubMed1994

Changes in vessel pressure and interstitial fluid pressure of normal subcutis and subcutaneous tumor in rats due to angiotensin II.

To elucidate the mechanism of enhancement of transport of anticancer drugs into tumor tissue due to angiotensin II (AII), changes in microvascular pressure (MVP) and interstitial fluid pressure (IFP) due to AII were measured in normal subcutis and subcutaneous tumor in rats. Two different tumor cell lines AH109A and AH272 were used. MVP and IFP were measured using a microocclusion method and a diffusion chamber method, respectively. Insignificant changes in the pressure of normal venous vessels and the IFP of normal subcutis were brought about by AII-induced hypertension. In both AH109A and AH272, the IFP of the same region within the tumor increased with enlargement of tumor volume. The IFP of AH109A tumor (tumor volume = 1.8-2.2 cm3) increased slightly due to AII, but the tumor MVP of AH109A and AH272 increased markedly. Though both tumor IFP and MVP increased significantly due to AII, the increases the hydrostatic pressure difference between tumor vascular and interstitial spaces and leads to enhancement of the efficiency of filtration from tumor vessels to tumor tissue, which is one of the mechanisms of enhancement of drug delivery to tumor tissue due to AII.

Angiotensin II↗