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S Tanda

Publications and source records attributed to S Tanda.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effects of intravenous infusion of dopamine on tumor blood flow in rat subcutis.

To determine the effects of intravenous administration of dopamine hydrochloride (DA) on tumor blood flow (TBF), we measured the blood flow of normal subcutaneous tissue and subcutaneous tumor (LY-80, a variant of Yoshida sarcoma) in enflurane-anesthetized male Donryu rats using a hydrogen clearance method. Measurements were made before and during intravenous infusion of DA at a rate of 5 micrograms/kg/min, while recording the mean arterial blood pressure of the rats. Under mild hypertension induced by DA, the blood flow of normal subcutis decreased and TBF increased significantly. SCH-23390, an antagonist of the DA1 receptor, inhibited the enhancement of TBF by DA; while domperidone, an antagonist of the DA2 receptor, did not modify the effects of DA. In experimental chemotherapy against the tumor using adriamycin (ADM) 5 mg/kg i.v., only the combination of DA and ADM significantly inhibited the tumor growth. Moreover, DA reduced the weight loss caused by ADM. These results indicate that DA could have a role in increasing TBF and possibly enhance drug delivery to tumors. Moreover, it appears that the DA1 receptor contributes, at least in part, to the enhanced blood flow in rat subcutaneous tumor following DA administration.

Animals↗
PubMed1994

The Drosophila tom retrotransposon encodes an envelope protein.

The tom transposable element of Drosophila ananassae is mobilized with high frequency in the germ line of females from the ca; px strain, and its insertion results in mutations that show almost exclusively dominant eye phenotypes. tom is a long terminal repeat-containing retrotransposon that encodes three different open reading frames (ORFs). It is expressed in the nurse cells during oogenesis, in the central and peripheral nervous systems during embryonic development, and in the imaginal discs of the larva. tom RNA accumulates in the germarium of ovaries from ca; px females but not in the parental inactive strain, suggesting that this altered pattern of tom expression might be the cause of the high rate of mobilization of this retrotransposon. The specificity of tom-induced eye phenotypes can be explained by the presence of regulatory sequences responsible for expression of tom in the eye imaginal discs of third-instar larvae. These sequences might cause overexpression of adjacent genes affected by tom-induced mutations, resulting in the death of undifferentiated cells located anterior to the morphogenetic furrow. In addition to the full-length RNA, tom is also transcribed into a spliced subgenomic transcript that encodes a protein resulting from the fusion between the amino-terminal region of the first (gag) and the third ORFs. The protein encoded by this RNA shows structural characteristics such as a signal peptide, glycosylation sites, endopeptidase cleavage site, and fusion peptide that are typical of the envelope proteins of retroviruses. Antibodies against tom ORF3 recognize two different proteins present in female ovaries, suggesting that tom might be able to form infective viral particles that could play a role in the horizontal transmission of this retrotransposon.

Amino Acid Sequence↗
PubMed1994

[Microvascular mechanisms of change in tumor blood flow elicited by vasopressors].

To elucidate the microvascular mechanisms of change in tumor blood flow due to vasopressors (angiotensin II, epinephrine, methoxamine), we analyzed the site of vascular resistance (VR) increased by each vasopressor. Arteriolar vessels within a transparent rat chamber were classified centripetally (a2-a5) according to Strahler's nomenclature. Vessels that feed into the tumor microcirculation were a2 modified by the tumor (starting vessels). Under angiotensin II (A II)-induced hypertension, the pressure of all arteriolar vessels increased roughly in proportion to the increase in mean arterial blood pressure. The greatest pressure drop and hence the most resistance due to A II occurred across the a2. During epinephrine-induced hypertension, there were major pressure drops between a4 and a3, and between a3 and a2. The amount of contraction of arteriolar vessels due to methoxamine was much smaller than that due to epinephrine, and the pressure increase in a4 and a3 was also small. From the facts described above, we may conclude as follows: A II creates greater vascular resistance of a2 vessels to blood flow and also greater perfusion pressure of a5-a3 vessels, resulting in increased blood inflow into a starting vessel which then becomes a passive vessel. Epinephrine causes an increase in the resistance of a3, a4 and probably upstream from a4 arterioles to blood flow. Thus, tissue blood flow in subcutis and tumor almost always decreases together. The fact that tissue blood flow in normal subcutis and tumor did not change significantly under methoxamine-induced hypertension is probably due to the results that methoxamine had little effects on the vascular resistance of smaller arterioles to blood flow.

Angiotensin II↗
PubMed1993

Microvascular mechanisms of change in tumor blood flow due to angiotensin II, epinephrine, and methoxamine: a functional morphometric study.

To elucidate the microvascular mechanisms of change in tumor blood flow elicited by vasopressors, a functional morphometric study of the s.c. microcirculation within a rat transparent chamber was performed. Arteriolar vessels were classified centripetally (a2-a5) according to Strahler's method. Arteriolar pressure in each segment both under normotension and under hypertension induced by angiotensin II, epinephrine, or methoxamine was measured using a microocclusion technique. Vasoconstriction was estimated by changes in vessel diameters. In addition, tissue blood flow of the subcutis and s.c. tumor (LY80, a variant of Yoshida sarcoma) under the same conditions was measured with the hydrogen clearance method. By comparing the sites of the greatest pressure drop and the vasoconstriction induced by each vasopressor, we assessed the sites of vascular resistance (VR) which showed increases due to these vasopressors. The greatest VR increase elicited by angiotensin II occurred across a2 vessels. On the other hand, the sites of VR increase due to epinephrine were in a3 vessels and larger vessels upstream from a3 arterioles. The VR increase induced by methoxamine was much smaller than that induced by epinephrine. We conclude that the fact that the sites of increased VR differ with each vasopressor is the primary reason that various vasopressors have been found to produce different changes in tumor blood flow.

Angiotensin II↗
PubMed1992

Circadian variation of tumor blood flow in rat subcutaneous tumors and its alteration by angiotensin II-induced hypertension.

Circadian fluctuation in tumor blood flow of the rat subcutaneous tumor was investigated. Tumor tissue blood flows in the daytime zone (10 a.m. to 4 p.m.) and in the nighttime zone (10 p.m. to 4 a.m.) in both the first phase (doubling time of tumor volume = 1.7 days) and the second phase (doubling time of tumor volume = 5.7 days) of growth of the LY80 tumor in rats were measured using the hydrogen gas clearance technique. In the first phase of tumor growth, the tumor blood flow was 20.3 +/- 12.2 ml/min/100 g in the daytime zone (n = 22) and 46.6 +/- 19.3 ml/min/100 g in the nighttime zone (n = 22). In the second phase, tumor blood flow was 9.6 +/- 5.7 ml/min/100 g in the daytime zone (n = 45) and 19.4 +/- 8.2 ml/min/100 g in the nighttime zone (n = 38). Tumor blood flow in the nighttime zone was significantly higher than that in the daytime zone (first phase, P less than 0.001; second phase, P less than 0.001). However, there were no significant differences in the mean arterial blood pressure, tumor size, and body weight of rats between the daytime zone and the nighttime zone. There was also a marked difference in the effect of angiotensin II-induced hypertension on tumor blood flow between the daytime zone and the nighttime zone. These results suggest that circadian fluctuations in tumor blood flow should be carefully considered when developing strategies to maximize the effectiveness of cancer therapy in relation to the flow rate of circulating blood.

Angiotensin II↗
PubMed1992

Mechanisms for appearance of no-flow areas in tumor microvascular bed.

In order to elucidate the mechanism for appearance of no-flow areas (areas where tumor blood flow temporarily cease), we directly observed the process of tumor-induced neovascularization and measured pressure change in a feeding vessel (starting vessel) which supplies blood to the tumor vascular network. Total length of tumor vascular network from one starting vessel increased exponentially as the tumor increased in size exponentially. The pressure of the starting vessel increased from approximately 40 cmH2O to 120 cmH2O with enlargement of the tumor size. As soon as the pressure of the starting vessel reached a plateau, however, there was a rapid increase in low-flow or no-flow areas in places within the tumor. We considered that no-flow areas were produced by the imbalance between the pressure elevation of a starting vessel and the enlargement of the vascular network from that vessel.

Animals↗
PubMed1991

Retrotransposon-induced overexpression of a homeobox gene causes defects in eye morphogenesis in Drosophila.

Insertion of the tom transposable element into various Drosophila ananassae genes results in dominant phenotypes that affect eye morphology. One of these genes encoded by the Om(1D) locus was isolated by transposon tagging. The Om(1D) gene encodes a 2.7 kb transcript that is expressed in every stage of development. The deduced Om(1D) protein is 606 amino acids long and contains two glutamine/histidine, two alanine-rich and one histidine/proline repeats, as well as a homeodomain located near the carboxy terminus. Tom-induced alleles of Om(1D) show a 1.7-fold increased accumulation of Om(1D) RNA in whole individuals during late larval--early pupal stages of development, whereas expression of this transcript is 7-fold higher in the eye--antenna imaginal disc of mutant versus wild-type flies. D. melanogaster flies transformed with the Om(1D) coding region under the control of the hsp70 promoter display an eye phenotype similar to that of Om(1D) when expression of the homeobox protein encoded by the chimeric gene is induced by temperature elevation at the end of the third instar period. These results suggest that the eye-specific mutant phenotype caused by the insertion of the tom retrotransposon in the Om(1D) locus may be a consequence of the tissue-specific induction of the expression of this gene by sequences present in the transposable element.

Amino Acid Sequence↗
PubMed1991

Characterization of heterogeneous distribution of tumor blood flow in the rat.

Angioarchitectures of ascites hepatoma AH109A and Sato lung carcinoma (SLC) were quantitatively compared by measuring the following morphometric parameters: vascular density, vascular length, distance between tissues and their nearest blood vessel, and total length of microvascular network per unit area. When the vascular networks in these two types of tumors were compared in the initial stage, the morphological parameters were almost identical. Correlations between tumor size and the number of starting vessels and between enlargement of the tumor and the ensuing increase in pressure of the starting vessel were also evaluated with a microcomputer and an apparatus for measuring microvascular pressure. The total length of tumor vascular network to which one starting vessel supplied blood increased exponentially as the tumor increased in size exponentially. There was a positive correlation between tumor size and the number of starting vessels. The range of the blood supply from one starting vessel was evidently limited. The pressure of the starting vessel increased with enlargement of the tumor size. As soon as the pressure of the starting vessel reached a plateau, however, there was a rapid increase in low-flow or no-flow areas in regions within the tumor. From the results obtained, we consider that low-flow or no-flow areas, resistant to delivery of anticancer drugs, inevitably appear with the progression of tumor growth.

Animals↗
PubMed1991

Fluctuations in tumor blood flow under normotension and the effect of angiotensin II-induced hypertension.

To elucidate the significance of angiotensin II (AII)-induced hypertension chemotherapy, changes of tissue blood flow both in normal subcutis and in tumors (AH109A, LY80) were measured with the hydrogen gas clearance method. A newly-developed anesthetic machine was used to keep the animals' condition constant. Tissue blood flow in normal subcutis and tumors always fluctuated with time under normotension. The nature and the rate of fluctuation in tumor blood flow were almost identical in two different types of tumors. However, the fluctuation of blood flow in tumor and that in normal subcutis were almost always inversely related when blood flows in these different tissues were measured simultaneously, i.e., when tissue blood flow in normal subcutis decreased, tumor blood flow increased, and vice versa. The findings supported the idea that the connection mode between the tumor vascular bed and normal vascular bed is a parallel circuit. Vascular resistance in the normal vascular bed under AII-induced hypertension seemed to be greater than that under normotension, because the AII-increased tumor blood flow always exceeded the maximum tumor blood flow under normotension. Due to the fluctuations of tumor blood flow, no-flow or low-flow areas, resistant to delivery of anti-cancer drugs, moved sporadically within the tumor under the normotensive condition. However, good conditions for drug delivery to tumor tissue were induced by AII-induced hypertension.

Anesthesia, Inhalation↗
PubMed1991

Comparison of the effects of intravenously bolus-administered endothelin-1 and infused angiotensin II on the subcutaneous tumor blood flow in anesthetized rats.

To evaluate the effects of endothelin-1 (ET-1) on tumor blood flow, the authors measured the mean arterial blood pressure (MABP) of enflurane-anesthetized male Donryu rats and the tissue blood flow of subcutaneously implanted tumor (Yoshida rat ascites hepatoma LY-80) by using a hydrogen clearance method. The tumor blood flow was evaluated in terms of the ratio to the maximum blood flow, which was defined as the largest flow in the same position during successive measurements. After bolus intravenous administration of ET-1 (1.0 nmol/kg), MABP reached approximately 140 mmHg (at 5-30 min), diminishing gradually to the baseline level over 2 h. The tumor blood flow increased from 36.7 +/- 20.6 to 59.5 +/- 30.2% (n = 32, P less than 0.001, at 2 min), returning to the baseline level at 10 min. On the other hand, at 2 min after the beginning of continuous intravenous infusion of [Asp1, Ile5]-angiotensin II (AII; the dose was determined by a blood pressure control system for keeping MABP at approximately 150 mmHg, consequently 0.26 micrograms/kg/min on the average), the tumor blood flow increased from 42.3 +/- 21.6 to 76.4 +/- 22.6% (n = 32, P less than 0.001), which was significantly larger than the flow after ET-1. The results indicate that hypertension induced by systemic ET-1 injection is less effective than hypertension induced by continuous systemic AII infusion in increasing tumor blood flow; AII is probably a suitable agent as a safe and effective enhancer of tumor blood flow. Moreover, ET-1 appears to constrict arterial vessels in the microcirculation time-dependently, while AII constricts probably only normal peripheral arterioles.

Anesthesia↗
PubMed1990

In vivo analysis of tumor vascularization in the rat.

By using transparent chambers in rats, we have directly observed tumor-induced neovascularization in the early stage and the formation of intricate networks in Yoshida rat ascites hepatoma AH109A and Sato lung carcinoma at high magnification. We counted branching point numbers per unit area in the microvascular network with and without tumors in order to clarify the sites from which new vascular sprouts originate. Branching point number per unit area in normal tissue was 13.6 +/- 7.4/0.1 mm2 in the field near a terminal arteriole, and 12.9 +/- 7.3/0.1 mm2 in the field distant from a terminal arteriole. There was no significant difference between these two fields in the normal vascular network. On the other hand, in the tumor vascular network, the branching point number in the field near a terminal arteriole was 50.4 +/- 12.6/0.1 mm2, and 30.1 +/- 11.5/0.1 mm2 in the field distant from a terminal arteriole. The difference is highly significant (P less than 0.001). The frequency with which new capillaries originated from veins and venules was very low. We concluded from these results that the position from which tumor vessels originated was usually the terminal portion of a terminal arteriole.

Animals↗
PubMed1990

[Development of the angioarchitecture and microcirculatory characteristics in rat tumor].

Using a rat transparent chamber and a device for measurement of microvascular pressure, we observed tumor vascularization process in vivo and measured the daily change in pressure of a "starting vessel" which supplies blood to the tumor vascular network. Results were summarized as follows: (1) The position from which tumor vessels originated was usually the terminal portion of a terminal arteriole (starting vessel). The frequency with which new capillaries originated from vein and venule was very low. (2) Pressure of a starting vessel increased from 30-40 cm H2O (22-30 mmHg) to 120-130 cm H2O (88-96 mmHg) with enlargement of the tumor vascular network. As soon as pressure of a starting vessel reached a plateau, no-flow vessels appeared in places within a tumor. (3) Pressure of a starting vessel was elevated by angiotensin II. In turn, the elevated pressure of a starting vessel brought about a marked increase in tumor blood flow, resulting in the blood flow in no-flow vessels.

Angiotensin II↗
PubMed1990

[The effects of angiotensin II and other noradrenergic vasoconstrictors on the blood flow in Yoshida rat ascites hepatoma AH 109 A at same electrode position].

The differing effects of angiotensin II (AT II) and five other vasoactive agents on the tissue blood flow in Yoshida rat ascites hepatoma AH 109 A were studied at the same electrode position by a hydrogen clearance method. The elevation of blood pressure by AT II resulted in a 3.4-fold increases in the tumor blood flow. However, when AT II was reinfused, it resulted in only 2.1, 2.2, 2.3, 1.9 and 2.4-fold increases, respectively, after infusion of methoxamine, norepinephrine, metaraminol, epinephrine, and phenylephrine. A pronounced reduction and further reducing tendency in the tumor blood flow were found after administration of norepinephrine and epinephrine. In addition, metaraminol, phenylephrine, and methoxamine did not change significantly the blood flow of the tumor. The results of this present blood flow study further suggest that AT II acts more peripherally in the host vascular bed from which newly growing tumor vessels bud than other vasoconstrictors do.

Adrenergic Agonists↗
PubMed1989

Analysis of the Om(1D) locus in Drosophila ananassae.

From the ca;px stock, which is the progenitor of Om mutants caused by insertions of the tom retrotransposon, 50 kb of genomic DNA including the Om(1D) locus was cloned by tom tagging and chromosome walking. Southern blot analyses of six Om(1D) mutants exposed one or two tom elements inserted at five nonrandom sites within an 18-kb distal segment of the restriction map; the phenotypic uniformity between these mutants was not affected by variations in the position, number or orientation of their inserts. Spontaneous revertants or more extreme derivatives of Om(1D) alleles were nonlinearly associated with losses or gains of tom inserts. Seven of eight radiation induced derivatives of Om(1D) mutants had one breakpoint of a chromosome rearrangement in polytene section 13A which includes the Om(1D) locus. Two Om(1D) derivatives, a spontaneous revertant and an induced extreme allele, were associated with overlapping deficiencies which define a region that is likely to contain the Om(1D) coding seguences proximal to the tom insertion sites. Incidental results confirm the previously indicated homology of the Om(1D) locus with the Bar locus of Drosophila melanogaster.

Animals↗
PubMed1989

Functional characteristics of tumor vessels: selective increase in tumor blood flow.

This experiment was carried out to elucidate how tumor microcirculation differs from that of normal tissues. Pressure-flow relationship was examined in normal rat tissues, uninvolved tissues in tumor-bearing rats, transplanted AH109A solid tumors, and primary tumors induced by 3-methylcholanthrene. Tumor blood flow was measured by the hydrogen clearance technique. The blood pressure was elevated by continuous iv infusion of angiotensin II. Elevation of blood pressure produced a several-fold increase in tumor blood flow without increasing blood flow in normal tissue and uninvolved tissue in tumor-bearing rats. The increase was selective to tumor tissues as long as the mean arterial blood pressure remained under about 150 mmHg. The lower the resting tumor blood flow, the greater the increase in the flow was at induced hypertension. There were no significant differences in the resting blood flow and in the rate of flow change at induced hypertension between the intramuscularly transplanted tumor, the intrahepatically transplanted tumor, and the sc transplanted tumor. These results indicate that the delivery of systemically administered anticancer drugs could be selectively enhanced in tumor tissues by induced hypertension.

Animals↗