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Biomedical subjects

K Ando

Publications and source records attributed to K Ando.

At least 361 records · Page 20Linked to original sources

Significance of platelets in an antimetastatic activity of bacterial lipopolysaccharide.

Recently we reported an antimetastatic activity of bacterial lipopolysaccharide (LPS) on a NK-cell-resistant murine fibrosarcoma (NFSa). Here we investigate and report the mechanistic significance of platelets in this activity. The number of circulating platelets was reduced to 63% of the control 3 days after an i.v. injection of 1.0 micrograms LPS, and then recovered to the level of control at day 10. Aggregation efficiency of platelets was impaired by LPS. The number of metastatic lung colonies after an i.v. injection of tumor cells was maximally reduced to 2.2% of the control at day 3 and increased in proportion to the recovery of platelet number. Neuraminidase (Ndase), which caused a non-immunological thrombocytopenia, also inhibited lung metastasis when injected prior to an i.v. tumor cell challenge. LPS and Ndase showed an identical pattern against five other syngeneic tumors; these agents inhibited lung metastases of the FSa fibrosarcoma and the SCC VII squamous cell carcinoma but failed to inhibit those of the NR-S1 squamous cell carcinoma, the MMCa#4 mammary adenocarcinoma and the NR-PG parotid gland tumor. All the three cells which were not responsive to any agents possessed a high aggregating activity of platelets while the other three tumors responsive to both agents did not show a detectable level of this activity. Platelet transfusion failed to modify the antimetastatic activity of LPS. These results suggest that platelets play an important role in the antimetastatic activity of LPS, though whether the role is principal or assistant remains to be seen.

Animals↗

Study on the suppressive effect of iodine-enriched egg on LT-C4 production in arachidonic acid-induced ear inflammation.

The anti-inflammatory mechanism of iodine-enriched egg was investigated in mice by means of arachidonic acid-induced ear inflammation. The lipid fraction of iodine-enriched egg was capable of suppressing the increase in ear weight induced by arachidonic acid in a dose-dependent manner. The lipid fraction was further separated into neutral and polar lipid fractions. Of these two fractions, only the neutral lipid fraction was capable of suppressing LT-C4 production in arachidonic acid inflammation. Neither the neutral nor polar lipid fractions of ordinary egg, however, showed any anti-inflammatory effect. These results suggest that the anti-inflammatory activity of iodine-enriched egg is present in the neutral lipid fraction, and its mechanism is assumed to be inhibition of LT-C4 production.

Animals↗

Detection of endothelin 1,2 and endothelin-like immunoreactant in wound surface and plasma in mice with thermal injury.

Endothelin is a well known vasoconstrictive peptides produced by endothelial cells and has been reported to regulate the systemic circulation. The authors investigated changes in endothelin in plasma and the surface of wounds induced with thermal injury using an experimental ear burn model in mice. At 0, 15, 30, 60, 120 and 180 minutes after thermal injury the plasma endothelin-like immunoreactant levels were 1.50 +/- 0.21, 1.86 +/- 0.36, 2.81 +/- 0.55, 2.62 +/- 0.27, 1.54 +/- 0.14 and 1.25 +/- 0.19 fmol/ml (N = 8), respectively. Endothelin-like immunoreactant levels in the plasma increased gradually until 30 minutes after the thermal injury. Endothelin-like immunoreactant content in the ear before thermal injury and at 60 minutes after injury were 7.04 +/- 0.64 and 8.61 +/- 1.24 fmol/ear (N = 8), respectively. The change in endothelin-like immunoreactant after thermal injury originated from endothelin 1,2; that is, the endothelin-1,2 content of the burned ear increased significantly 15 and 60 minutes after thermal injury to 12.52 +/- 0.68 and 11.58 +/- 1.04 fmol/ear, respectively, compared with 1.78 +/- 0.91 fmol/ear (N = 8) obtained before injury. These results suggested that endothelin 1,2 existed in the region of the wound caused by thermal injury.

Animals↗

Involvement of prostaglandins and renal haemodynamics in salt-sensitivity of young spontaneously hypertensive rats.

OBJECTIVES: To clarify the involvement of prostaglandins and renal haemodynamics in the pathogenesis of salt-induced hypertension. DESIGN: Young (6-week-old) spontaneously hypertensive rats (SHR), a salt-sensitive hypertensive model, were used. METHODS: The effect of long-term (4-week) administration of cicletanine (50 mg/100 g in the diet), which stimulates prostaglandins synthesis, was examined concerning the development of hypertension in young SHR fed on 8% salt-containing diet. Whether the cyclo-oxygenase inhibitor indomethacin (3.0 mg/kg per day for the last 4 days of the treatment) attenuates the hypertension was also studied. Renal haemodynamics were examined by clearance of inulin (glomerular filtration rate) and para-aminohippurate (renal plasma flow). RESULTS: Salt loading significantly accelerated the development of hypertension, and the salt-induced blood pressure rise was significantly attenuated by cicletanine, although cicletanine did not attenuate the spontaneous development of hypertension. The hypotensive effect of cicletanine was abolished by indomethacin. Glomerular filtration rate and renal blood flow were not changed with these treatments. However, the changes in renal vascular resistance were parallel to those in mean blood pressure: it was increased with salt loading, reversed by cicletanine and increased by indomethacin. Salt loading decreased urinary prostaglandin E2, cicletanine reversed the effect of salt loading and indomethacin inhibited the effect of cicletanine. CONCLUSIONS: The present findings suggest that the abnormality in prostaglandin E2 contributes to the increased salt sensitivity in young SHR, probably through renal haemodynamic changes.

Animals↗

Linear lichen planus mimicking creeping eruption.

A 42-year-old woman was referred to our hospital with a linear eruption on her right flank of two months duration. Because she had eaten loach-fish a month before she noticed the eruption, a creeping eruption due to Gnathostoma spp. was initially suspected, but the histological findings of the biopsy specimens showed typical features of lichen planus. Linear lichen planus is discussed based on the cases accumulated in the literature regarding the distribution of Blaschko lines.

Adult↗

Differential alterations of dihydrofolate reductase gene in human leukemia cell lines made resistant to various folate analogues.

In order to clarify a molecular mechanism of folate resistance in leukemia cells, we studied alterations of the dihydrofolate reductase (DHFR) gene in a human leukemia cell line, MOLT-3, and its sublines made resistant to methotrexate (MTX), trimetrexate (TMQ) and N10-propargyl-5,8-dideazafolic acid (CB3717), alone or in combination. Major alterations of the DHFR gene were examined by Southern analysis of high-molecular-weight DNA. The presence of a base change (T-->C) at nucleotide position 91 of the DHFR gene, which is reported to be responsible for the reduced affinity of the enzyme for MTX in an MTX-resistant human colon carcinoma cell, was examined by allele-specific oligonucleotide hybridization. In a 10,000-fold MTX-resistant subline (MOLT-3/MTX10,000), the normal allele of DHFR gene had been amplified. In contrast, a 200-fold TMQ-resistant subline (MOLT-3/TMQ200) and a 30-fold CB3717-resistant subline selected from MOLT-3/TMQ200 (MOLT-3/TMQ200-CB-3717(30)) were shown to have the mutant allele. Furthermore, the mutant allele had been amplified in a 500-fold MTX-resistant subline, which was established by the continuous exposure of the MOLT-3/TMQ200 cells to stepwise increases of drug concentration and designated as MOLT-3/TMQ200-MTX500. On the other hand, a 40-fold-resistant subline to CB3717 alone (MOLT-3/CB3717(40)) showed the normal allele without amplification. These data suggest that complex alterations of the DHFR gene are involved in the molecular mechanisms of folate resistance that can be differentially introduced into leukemia cells by exposure to various folate analogues, alone or in combination.

Antineoplastic Agents↗

Long-term course of adult patients with delayed sleep phase syndrome.

A response to treatment and long-term course of 14 adults with delayed sleep phase syndrome were investigated with the use of their hospital records and mailed questionnaires. Six patients treated with chronotherapy showed full recovery just after the treatment. In three of them the delay of sleep phase relapsed one year afterwards. Four of five patients treated with pharmacotherapy alone showed partial recovery. Six of nine patients followed for periods of longer than three years after treatment showed good prognoses, though all of them still had a mild phase delay and had to shorten their sleep time in order to work full-time. The three others had poor prognoses and one of them was under psychiatric treatment for affective instability. These findings suggest that a long-term follow-up is needed to judge the effect of the treatment.

Activities of Daily Living↗

Enhancement of vasoconstrictor response by a noncalcemic analogue of vitamin D3.

To clarify the effects of active vitamin D3 on pressor and vascular responses to vasoconstrictor substances, we studied pressor responses to the intravenous injection of norepinephrine or angiotensin II (Ang II) and vasoconstrictor responses to norepinephrine. Sprague-Dawley rats were given 1,25-dihydroxyvitamin D3 subcutaneously (200 ng/kg per day) for 14 days. The administration of 1,25-dihydroxyvitamin D3 augmented the pressor responses to norepinephrine and Ang II in conscious rats and was associated with a significant increase in serum calcium concentration (11.0 +/- 0.2 mg/dl). To further clarify whether the increased pressor response to vasoconstrictors may be due to the calcemic or direct action of active vitamin D3, we studied the effect of its noncalcemic analogue, 22-oxacalcitriol, and its inactive analogue, 24,25-dihydroxyvitamin D3, on the pressor response to vasoconstrictors in rats. The pressor responses to norepinephrine and Ang II were apparently augmented in 22-oxacalcitriol-treated rats similarly to 1,25-dihydroxyvitamin D3-treated rats. In contrast, the pressor responses were not affected by either 24,25-dihydroxyvitamin D3 or the intravenous infusion of calcium chloride. In an ex vivo experiment using a mesenteric preparation, the vascular sensitivity to norepinephrine was moderately augmented in rats treated with both 22-oxacalcitriol and 1,25-dihydroxyvitamin D3 but was not affected in rats treated with 24,25-dihydroxyvitamin D3. The results suggest that the enhanced pressor responses to norepinephrine and Ang II could be attributed to the direct effect of active vitamin D3 on vasculature rather than to hypercalcemia.

24,25-Dihydroxyvitamin D 3↗

AS-183, a novel inhibitor of acyl-CoA: cholesterol acyltransferase produced by Scedosporium sp. SPC-15549.

A novel compound, AS-183, which inhibits acyl-CoA: cholesterol acyltransferase (ACAT), was isolated from the culture broth of a fungus, Scedosporium sp. SPC-15549. AS-183 inhibited ACAT activity in an enzyme assay system using rabbit liver microsomes with an IC50 value of 0.94 microM. AS-183 also inhibited cholesterol ester formation in HepG2, CaCo2, and THP-1 cells with IC50 values of 18.1, 25.5, and 34.5 microM, respectively.

Animals↗

MS-347a, a new inhibitor of myosin light chain kinase from Aspergillus sp. KY52178.

MS-347a was isolated from the culture broths of Aspergillus sp. KY52178 as an inhibitor of smooth muscle myosin light chain kinase (MLCK). MS-347a inhibited the activity of chicken gizzard MLCK with an IC50 value of 9.2 microM. The inhibition was dependent on time of preincubation of MS-347a with the enzyme, suggesting irreversible inhibition. It is likely that the inhibitor binds to the catalytic domain of MLCK, since the compound inhibited not only calmodulin-dependent but also calmodulin-independent activity of MLCK. Calmodulin-dependent cyclic nucleotide phosphodiesterase, cAMP-dependent protein kinase and cGMP-dependent protein kinase were not inhibited by 150 microM MS-347a at all, although the compound inhibited protein kinase C with an IC50 value of 16 microM. MS-347b, a minor component was also isolated from the same culture broths. This minor component at 150 microM did not inhibit the activity of MLCK.

Aspergillus↗

Effect of prostaglandin E on the redistribution of lysosomal enzymes in caerulein-induced pancreatitis.

The redistribution of cathepsin B, a representative lysosomal enzyme, from the lysosomal pellet to the zymogen pellet in subcellular fractions and the colocalization of cathepsin B with digestive enzymes within acinar cells have been found during the early stage of caerulein-induced acute pancreatitis in the rat. This study investigated the protective effects of prostaglandins E1 and E2 on the exocrine pancreas in this experimental pancreatitis. Prostaglandin E2, but not E1, prevented the redistribution of cathepsin B along with the hyperamylasemia, and the increase in amylase and trypsinogen in the acinar cells in almost a dose-dependent manner, particularly at a dose of 100 micrograms/kg.hr of continuous infusion. These results suggest that subcellular organelle fragility is closely related to the pathogenesis of acute pancreatitis, and that prostaglandin E2 has an important cytoprotective effect on biological membranes as a stabilizer of lysosomal membrane.

Alprostadil↗

The discriminative effects of nicotine and their central sites in rats.

The mediations in the central sites of the discriminative effects of nicotine were studied. Rats were trained to discriminate between the effects of nicotine at 0.5 mg/kg, sc and saline under a fixed ratio 10 schedule, for food reinforcement in a 2-lever operant chamber situation. After the establishment of discrimination behavior, guide cannulae were implanted bilaterally into the lateral ventricle (n = 10), the nucleus accumbens (n = 11), the ventral tegmental area (n = 7), and the dorsal hippocampus (n = 9). In substitution tests, nicotine at 100 and 120 micrograms per rat administered into the lateral ventricle and this drug at 100 micrograms per rat administered into the nucleus accumbens substituted for subcutaneous nicotine. On the other hand, neither nicotine at 10-80 micrograms per rat administered into the ventral tegmental area, nor this drug at 5-20 micrograms per rat administered into the dorsal hippocampus substituted for the subcutaneous nicotine. In antagonism tests, mecamylamine was administered into each brain area in combination with nicotine at 0.5 mg/kg, sc. Mecamylamine at 180 micrograms per rat administered into the nucleus accumbens blocked the discriminative effects of the subcutaneous nicotine while mecamylamine, administered into the ventral tegmental area and the dorsal hippocampus, did not. These results may indicate that the discriminative effects of subcutaneous nicotine are at least partially mediated in the nucleus accumbens.

Animals↗

Effect of prostaglandin E2 on cellular, lysosomal and mitochondrial fragility in caerulein-induced pancreatitis in rats.

The effects of prostaglandin E2 on the fragility of cellular and subcellular organelles in caerulein-induced acute pancreatitis were investigated in rats. PGE2 at doses of 50 and 100 micrograms/kg/hr infused for 2 hours before and during caerulein (5 micrograms/kg/hr for 3.5 hours) infusion significantly prevented the increased discharge of both amylase and lactate dehydrogenase from dispersed acini, and the leakage of cathepsin B from lysosomes and of malate dehydrogenase from mitochondria in the subcellular fraction in vitro. These results suggest that PGE2 has a cytoprotective effect against caerulein-induced pancreatitis by stabilizing cell and lysosomal and mitochondrial membranes.

Acute Disease↗

[Type IV collagenase activities in human colorectal cancers and its role in cancer invasion and metastasis].

In 36 patients with colorectal cancers, type IV collagenase activities were measured in cancer and non-cancer tissues for evaluating its role in the process of cancer invasion and metastasis. The colorectal cancer tissues revealed remarkably higher activities than the distant normal and tumor-neighboring mucosa (p < 0.001). The activities in the colorectal cancer tissues with high-grade histological venous invasion were higher than those with low-grade histological venous invasion (p < 0.005). But no differences of the activities were found between patients with and without hepatic metastasis. These results suggest that the type IV collagenase plays an important role in the cancer invasion to the blood vessels around the primary site in colorectal cancers.

Adult↗

[The study on mechanism of abruptio placentae caused by chorioamnionitis].

The cause of abruptio placentae has not been elucidated yet. Although preeclampsia is frequently associated with abruptio placentae, the rate of abruptio placentae caused by preeclampsia has decreased recently. Many current reports have indicated that chorioamnionitis is an important cause of abruptio placentae. To clarify the relationship between chorioamnionitis and abruptio placentae, we performed immunostaining for fibronectin, fibronectin receptor and granulocyte elastase of placenta with or without abruptio placentae. In cases of abruptio placentae caused by chorioamnionitis, granulocyte elastase was stained strongly and fibronectin receptor was stained weakly in decidual cells, especially in the parts of granulocyte elastase invased. In III stage chorioamnionitis without abruptio placentae, granulocyte elastase was stained moderately and the intensity of fibronectin receptor did not decrease. There was no difference between fibronectin staining in all cases. When purified granulocyte elastase was added to the cultured decidual cells, the staining intensity of fibronectin receptor became weak in those cells. These results suggest that marked imbalance between neutrophil invasion and an inhibitor, such as alpha 1 antitrypsin, initiates granulocyte elastase release and promotes the reduction of the fibronectin receptor in decidual cells resulting in weakening of the adherence of decidual cells. This may be one of the mechanisms of abruptio placentae caused by chorioamnionitis.

Abruptio Placentae↗