Biomedical subjects

N Sasaki

Publications and source records attributed to N Sasaki.

At least 109 records · Page 6Linked to original sources

PubMed2000

Course before and after percutaneous transhepatic portal vein embolization of a patient with cholangiocarcinoma monitored by scintigraphy with Tc-99m galactosyl human serum albumin.

Percutaneous transhepatic portal vein embolization (PTPE) causes atrophy of the embolized lobe and compensatory hypertrophy of the nonembolized lobe, and improves the safety of hepatectomy. We report a patient with cholangiocarcinoma who underwent embolization of both anterior and posterior branches of the right portal vein before hepatectomy. Scintigraphy with Tc-99m galactosyl human serum albumin was performed before and 4 weeks after PTPE. After PTPE, the right lobe of the liver was atrophied and the left lobe of the liver was enlarged, compared with before PTPE. The receptor index of the entire liver was almost unchanged before and after PTPE, but the right lobe receptor index after PTPE was 23% less than the pre-PTPE value, whereas the left lobe receptor index had increased 37%. Scintigraphy with Tc-99m galactosyl human serum albumin is useful for evaluating segmental functional reserve before and after PTPE.

Aged↗

PubMed2000

Clinical usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose in the diagnosis of liver tumors.

We studied various liver tumors by positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) to examine the diagnostic usefulness of this technique. We also examined the relation between findings on FDG-PET and the characteristics of hepatocellular carcinoma. FDG-PET was performed in 78 patients with liver tumors, including 53 with primary liver cancer [48 hepatocellular carcinomas (HCC) and 5 cholangiocellular carcinomas (CCC)], 20 with metastatic liver cancer, 2 with liver hemangioma, and 3 with focal nodular hyperplasia. For quantitative evaluation, a region of interest (ROI) was placed over the entire tumor region, at the level of the maximum diameter of the tumor. A background ROI was then placed over the non-tumor region of the liver. The average activity within each ROI was subsequently corrected for radioactive decay, and the standardized uptake value (SUV) was calculated by dividing the tissue activity by the injected dose of radioactivity per unit body weight. SUV ratio was expressed as the tumor-to-non-tumor ratio of the SUV. The median SUV was significantly lower in HCC than in metastatic live cancer or CCC, and the median SUV ratio was significantly lower in HCC than in metastatic liver cancer or CCC. The median SUV was not higher in multiple HCC than in single HCC, but the median SUV ratio was significantly higher in multiple HCC than in single HCC. The median SUV and the median SUV ratio were significantly higher in the presence of portal vein thrombosis than in the absence of such thrombosis. The Cancer of the Liver Italian Program score and the alpha-fetoprotein value correlated significantly with both the SUV and SUV ratio. These results suggest that FDG-PET is clinically useful not only for the differential diagnosis of liver tumors but also for evaluation of the clinical characteristics of HCC.

Adult↗

PubMed2000

A case of cavernous hemangioma of the small intestine diagnosed by scintigraphy with Tc-99m-labeled red blood cells.

Hemangioma of the small intestine is rare, and the preoperative diagnosis of it is difficult. We report a patient with gastrointestinal bleeding for whom Tc-99m-labeled red blood cell scintigraphy was useful in diagnosing cavernous hemangioma of the small intestine. A 25-year-old man was referred to our hospital for recurrent iron deficiency anemia. Because of the patient's severe anemia, imaging was performed to locate the bleeding lesion in the gastrointestinal tract. Scintigraphy with Tc-99m-labeled red blood cells revealed pooling indicating a tumor and extravasation of blood from the tumor. Scintigraphy with Tc-99m pertechnetate revealed no abnormal accumulation. Partial resection of the small intestine was done, and cavernous hemangioma of the small intestine was diagnosed by using the specimen of resected tissue.

Adult↗

PubMed2000

A case of recurrent cholangitis after bile duct injury during laparoscopic cholecystectomy: value of scintigraphy with Tc-99m GSA and hepatobiliary scintigraphy for indication of lobectomy.

A 39-year-old woman with acute cholecystitis and gallstones underwent laparoscopic cholecystectomy. She suffered from recurrent episodes of cholangitis due to injury of the major bile ducts during laparoscopic cholecystectomy. Hepatobiliary scintigraphy with Tc-99m Sn-N-pyridoxyl-5-methyltryptophan was performed. Although normal bile excretion was found from the left hepatic duct to the percutaneous transhepatic biliary drainage (PTBD) tube, excretion from the right hepatic lobe was prolonged. Scintigraphy with Tc-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin demonstrated atrophy of the right hepatic lobe and enlargement of the left hepatic lobe. Cholangiography via the PTBD tube revealed complete obstruction of the left hepatico-jejunal anastomosis and could not enhance the right intrahepatic bile duct. A right hepatic lobectomy was performed because of the atrophy, glissonitis and the absence of an appropriate bile duct for reconstruction. Postoperatively she was active and exhibited no evidence of recurrent cholangitis.

Adult↗

PubMed2000

In vitro DNA fragmentation of mitochondrial DNA caused by single-stranded breakage related to macroplasmodial senescence of the true slime mold, Physarum polycephalum.

We found that mitochondrial DNA (mtDNA) isolated from Physarum polycephalum fragmented itself in weak ionic solutions. The mtDNA was dissolved in STE (saline Tris-EDTA: 150 mM NaCl, 10 mM Tris-HCl, 1 mM EDTA), TE (10 mM Tris-HCl, 1 mM EDTA) and DW, and then electrophoresed in an agarose gel. The intact 86-kbp mtDNA band was seen in STE, but several novel bands appeared in TE and DW. In TE, two discrete bands appeared at 6.7-kbp (alpha-band) and 5.0-kbp (beta-band), whereas at least 17 discrete bands were observed in distilled water (DW). These fragmentation patterns were not stoichiometric, as seen when using restriction endonucleases, but were clearly different from the degradation of DNA caused by a physical shearing force or a contaminating nuclease. In this paper, we characterize this in vitro fragmentation of mtDNA from P. polycephalum. We located 19 fragments, including the alpha and beta fragments, on a mtDNA restriction map, and demonstrated that these cleavage sites were S1 nuclease-sensitive regions, which are single-stranded DNA regions such as nicks and gaps in the mtDNA. The alpha and beta fragments are derived from the region encoding ribosomal RNAs (rRNAs) and the ATP synthase (atpA) gene, while the other 17 fragments are not derived from any specific region, but the cleavage sites are located throughout the mtDNA molecule. In P. polycephalum, it is well known that the growth rate of macroplasmodia decreases with aging. Equal amounts of mtDNA from juvenile and aged macroplasmodia were electrophoresed and the frequency of the beta fragment in each sample was measured. The ratio of the beta band to the total signal including background was estimated to be 3.3-4.0% in juvenile macroplasmodia, whereas it increased to 8.3-28.2% in aged macroplasmodia. This result suggests that the in vitro fragmentation of mtDNA is associated with macroplasmodial senescence. The single-stranded breakage of mtDNA of P. polycephalum may accumulate with age.

Aging↗

PubMed2000

Block of sodium channels by divalent mercury: role of specific cysteinyl residues in the P-loop region.

Divalent mercury (Hg(2+)) blocked human skeletal Na(+) channels (hSkM1) in a stable dose-dependent manner (K(d) = 0.96 microM) in the absence of reducing agent. Dithiothreitol (DTT) significantly prevented Hg(2+) block of hSkM1, and Hg(2+) block was also readily reversed by DTT. Both thimerosal and 2,2'-dithiodipyridine had little effect on hSkM1; however, pretreatment with thimerosal attenuated Hg(2+) block of hSkM1. Y401C+E758C rat skeletal muscle Na(+) channels (mu1) that form a disulfide bond spontaneously between two cysteines at the 401 and 758 positions showed a significantly lower sensitivity to Hg(2+) (K(d) = 18 microM). However, Y401C+E758C mu1 after reduction with DTT had a significantly higher sensitivity to Hg(2+) (K(d) = 0.36 microM) than wild-type hSkM1. Mutants C753Amu1 (K(d) = 8.47 microM) or C1521A mu1 (K(d) = 8.63 microM) exhibited significantly lower sensitivity to Hg(2+) than did wild-type hSkM1, suggesting that these two conserved cysteinyl residues of the P-loop region may play an important role in the Hg(2+) block of the hSkM1 isoform. The heart Na(+) channel (hH1) was significantly more sensitive to low-dose Hg(2+) (K(d) = 0.43 microM) than was hSkM1. The C373Y hH1 mutant exhibited higher resistance (K(d) = 1.12 microM) to Hg(2+) than did wild-type hH1. In summary, Hg(2+) probably inhibits the muscle Na(+) channels at more than one cysteinyl residue in the Na(+) channel P-loop region. Hg(2+) exhibits a lower K(d) value (<1. 23 microM) for inhibition by forming a sulfur-Hg-sulfur bridge, as compared to reaction at a single cysteinyl residue with a higher K(d) value (>8.47 microM) by forming sulfur-Hg(+) covalently. The heart Na(+) channel isoform with more than two cysteinyl residues in the P-loop region exhibits an extremely high sensitivity (K(d) < 0. 43 microM) to Hg(+), accounting for heart-specific high sensitivity to the divalent mercury.

2,2'-Dipyridyl↗

PubMed2000

Marriage rate and number of children among young adults with insulin-dependent diabetes mellitus in Japan.

The main purpose of our study was to identify the social circumstances and lifestyle of IDDM patients in Japan. The present study focused on the marriage status of both men and women with IDDM as well as the number of children of women with IDDM. A questionnaire was sent to hospitals across the country. Doctors handed it or mailed it to IDDM patients aged 18 years or older. Unsigned answer sheets were returned directly by the patients. Data on the marriage rate and number of children were obtained, and possible factors affecting these indices were assessed. One thousand and thirteen patients (354 men and 659 women) answered the questionnaire. Both men and women with IDDM were less likely to be married in comparison with age-matched Japanese. The number of children of married IDDM women in various age groups was also lower in comparison with the general Japanese female population. Several factors other than diabetes complications including job discrimination, high medical costs, and psychological pressures, were thought to be responsible for these results.

Adult↗

PubMed2000

Effects of contralateral noise on measurement of the psychophysical tuning curve.

The effects of the addition of contralateral noise on the psychophysical tuning curve (PTC) were examined in subjects with normal hearing. The masking threshold of the tail part of the PTC tended to decrease with the addition of contralateral noise, although the threshold reduction was usually less than 5 dB. On the other hand, the effects of contralateral noise were relatively small around the tip of the PTC contour. Focusing on the effects of contralateral noise on the masking threshold at the tail part of the PTC, the effects of changing the time between initiation of masking the tone and the presentation of the masked probe tone on the threshold reduction at the tail part of the PTC were also observed. The results indicate that the reduction of the masking threshold by the addition of contralateral noise tended to be larger when the presentation of the signal tone was delayed after the onset of the masker. Usually, when the signal tone was presented under conditions of the forward masking paradigm, the reduction of the threshold was most remarkable. Results obtained in the present study are discussed based on the known characteristics of the olivocochlear (OC)-efferent fibers activated by contralateral noise.

Adult↗

PubMed2000

Nicorandil, a potent cardioprotective agent, acts by opening mitochondrial ATP-dependent potassium channels.

OBJECTIVES: To determine the mechanism of cardioprotection afforded by nicorandil, an orally efficacious antianginal drug, we examined its effects on ATP-dependent potassium (K(ATP)) channels. BACKGROUND: Nicorandil can mimic ischemic preconditioning, while mitochondrial K(ATP) (mitoK(ATP)) channels rather than sarcolemmal K(ATP) (surfaceK(ATP)) channels have emerged as the likely effectors. METHODS: Flavoprotein fluorescence and membrane current in intact rabbit ventricular myocytes were measured simultaneously to assay mitoK(ATP) channel and surface K(ATP) channel activities, respectively. In a cell-pelleting model of ischemia, cells permeable to trypan blue were counted as killed by 60 and 120 min of ischemia. RESULTS: Nicorandil (100 micromol/liter) increased flavoprotein oxidation but not membrane current; a 10-fold higher concentration recruits both mitoK(ATP) and surfaceK(ATP) channels. Pooled dose-response data confirm that nicorandil concentrations as low as 10 micromol/liter turn on mitoK(ATP) channels, while surfaceK(ATP) current requires exposure to millimolar concentrations. Nicorandil blunted the rate of cell death in a pelleting model of ischemia; this cardioprotective effect was prevented by the mitoK(ATP) channel blocker 5-hydroxydecanoate but was unaffected by the surfaceK(ATP) channel blocker HMR1098. CONCLUSIONS: Nicorandil exerts a direct cardioprotective effect on heart muscle cells, an effect mediated by selective activation of mitoK(ATP) channels.

Adenosine Triphosphate↗

PubMed2000

Type 1A dopamine receptor expression in the heart is not altered in spontaneously hypertensive rats.

We have recently demonstrated that type 1A dopamine (D1A) receptor is expressed in the rat heart, but its function still remains unknown. In the present study, we investigated possible changes in the expression level and the distribution of the cardiac D1A receptor in the development of left ventricular hypertrophy in spontaneously hypertensive rats/Izumo strain (SHR/Izm) at the ages of 4, 8, and 20 weeks. We examined D1A receptor protein distribution by immunohistochemistry and gene expression by competitive polymerase chain reaction (competitive PCR). In SHR/Izm, compared with the age-matched Wistar Kyoto rats/Izmo strain (WKY/Izm), blood pressure and heart/body weight ratio were significantly increased at 8 and 20 weeks. By immunohistochemistry, the D1A receptor was localized in cardiomyocytes and vascular smooth muscle cells of coronary arteries, but not in interstitial fibrotic tissue. D1A receptor distribution was not changed either by the strain or the age. Competitive PCR analysis showed that the D1A receptor mRNA level was significantly higher at 4 weeks than at 8 and 20 weeks in both strains of rats and that there was no significant difference in D1A receptor mRNA between SHR/Izm and WKY/Izm at any age (43.2 +/- 10.4 attomol x 10(-3)/L v 43.1 +/- 11.2 attomol x 10(-3)/L at 4 weeks, P = not significant, 3.9 +/- 0.9 attomol x 10(-3)/L v 4.0 +/- 1.3 attomol x 10(-3)/L at 8 weeks, P = not significant, 3.0 +/- 1.2 attomol x 10(-3)/L v 1.9 +/- 1.6 attomol x 10(-3)/L at 20 weeks, P = not significant). These results do not support the hypothesis that changes in D1A receptor expression are associated with the development of left ventricular hypertrophy in SHR.

Animals↗

PubMed2000

Use of floating alginate gel beads for stomach-specific drug delivery.

Two types of alginate gel beads capable of floating in the gastric cavity were prepared. The first, alginate gel bead containing vegetable oil (ALGO), is a hydrogel bead and its buoyancy is attributable to vegetable oil held in the alginate gel matrix. The model drug, metronidazole (MZ), contained in ALGO was released gradually into artificial gastric juice, the release rate being inversely related to the percentage of oil. The second, alginate gel bead containing chitosan (ALCS), is a dried gel bead with dispersed chitosan in the matrix. The drug-release profile was not affected by the kind of chitosan contained in ALCS. When ALCS containing MZ was administered orally to guinea pigs, it floated on the gastric juice and released the drug into the stomach. Furthermore, the concentration of MZ at the gastric mucosa after administration of ALCS was higher than that in the solution, though the MZ serum concentration was the same regardless of which type of gel was administered. These release properties of alginate gels are applicable not only for sustained release of drugs but also for targeting the gastric mucosa.

Alginates↗

PubMed2000

T7 RNA polymerase activation and improvement of the transcriptional sequencing by polyamines.

We examined the possibility to improve the effectiveness of the in vitro transcription system using T7 RNA polymerase by coexistence with organic bases. The effect of the additives was evaluated by measuring the amount of RNA products in comparison with that of the control system (without additive). We found that four commercial bases and a series of ethylated polyamine analogues newly designed were active enhancers in the following activation order, 1,8-bis(ethylamino)octane > 1,8-octanediamine > 1,5-bis(ethylamino)pentane > cadaverine > 1,8-bis(ethylamino)-4-azaoctane > spermidine 1,18-bis(ethylamino)-5,14-diazaoctadecane > agmatine. It was shown that RNA products were corresponding, only in the presence of active enhancers, to the full length size of the template DNA, and that sequencing signals were enhanced by the presence of active enhancers with high fidelity so that the transcriptional sequencing was further refined to be a highly sensitive sequencing method from a small amount of linear dsDNA. These results suggest that T7 RNA polymerase was activated by the specific binding of the polyamine additive to produce RNA transcripts with fidelity to the template DNA. Therefore, it is expected that the transcriptional sequencing in the presence of active enhancers might be a powerful and sensitive method, in place of the prevalent DNA amplification method, for genomic science projects and clinical and practical gene diagnoses.

DNA↗

PubMed2000

p53, bcl-2 and bax abnormalities in non-Hodgkin's lymphomas of the head and neck.

In the present study, mutations or protein expression of p53, bcl-2 and bax are reported in 13 non-Hodgkin's B-cell lymphomas of the head and neck. Nine of 13 cases (69.2%) expressed p53 protein and 7 (53.8%) showed gene mutations. On comparing the results of immunostaining and SSCP analysis, there were two cases showing discrepancies between the p53 protein expression and gene mutations. Bcl-2 protein expression was observed in only two cases of follicular lymphoma. On the other hand, bax protein was detected in all 13 cases. One case with mutated bax gene showed a lower expression with a reduced frequency of bax-positive cells than the other 12. These results suggest that inactivation of p53 may be closely related to development and/or progression of these NHLs, and that bcl-2 and bax protein may not have a role.

Adolescent↗

PubMed2000

Selective action of a CCK-B/gastrin receptor antagonist, S-0509, on pentagastrin-, peptone meal- and beer-stimulated gastric acid secretion in dogs.

BACKGROUND: The pharmacological effects of a novel CCK-B/gastrin receptor antagonist, S-0509, on gastric acid secretion in dogs remain unknown. AIM: To evaluate the antisecretory effects of S-0509 on gastric acid secretion and to compare such effects with famotidine or atropine in dogs stimulated with various gastric stimulants. METHODS: Ten beagle dogs with a denervated Heidenhain pouch and three beagle dogs with an innervated gastric fistula were used. Gastric acid secretion was stimulated by either continuous intravenous administration of pentagastrin, carbachol or histamine, or oral administration of a peptone meal or beer. RESULTS: In the Heidenhain pouch model, both intravenously administered and orally administered S-0509 significantly inhibited the gastric acid secretion stimulated by pentagastrin, peptone meal and beer. Nonetheless, the drug had little or no effect on carbachol-stimulated or histamine-stimulated acid secretion. Famotidine extensively inhibited all gastric acid secretion stimulated by the above stimulants in a non-selective manner. Atropine also significantly inhibited the acid secretion stimulated by pentagastrin, peptone meal, beer or carbachol, but was not able to inhibit stimulation due to histamine. Oral administration of peptone meal or beer significantly increased the plasma gastrin level. Similarly to the Heidenhain pouch model, even in the gastric fistula (GF) model, S-0509 significantly inhibited pentagastrin-stimulated gastric acid secretion, yet the drug had no effect on carbachol-stimulated secretion. CONCLUSIONS: S-0509 is a selective CCK-B/gastrin receptor antagonist in dogs that inhibits gastric acid secretion stimulated by pentagastrin and gastrin-releasing substances, but does not inhibit histamine-stimulated and carbachol-stimulated acid secretion.

Animals↗

PubMed2000

Changes in Helicobacter pylori-induced gastritis in the antrum and corpus during long-term acid-suppressive treatment in Japan.

BACKGROUND: Several studies have shown that acid-suppressive therapy aggravates corpus gastritis in patients with Helicobacter pylori infection, promoting the development of atrophic gastritis. AIM: To study the effects of long-term use of antisecretory agents on the H. pylori-positive gastric mucosa in Japan, a country with a high incidence of gastric cancer. METHODS: A total of 141 H. pylori-positive patients who had peptic ulcers or reflux oesophagitis were treated for 3 years with either omeprazole (20 mg/day) alone (n=7) or with omeprazole for primary therapy (8 weeks), followed by famotidine (40 mg/day) for maintenance therapy (n=134). Endoscopy was performed before, during, and after treatment. Biopsy specimens were taken from the greater curvature of the antrum and corpus and were examined histologically. RESULTS: The long-term use of famotidine after 8 weeks of treatment with omeprazole distinctly decreased H. pylori density and neutrophil infiltration in the antrum, but did not change H. pylori density in the corpus. The gastritis score increased in patients who had no, or only mild corpus gastritis before treatment (n=74), and significantly decreased in those who had moderate or severe gastritis before treatment (n=60). In four of the seven patients who received long-term treatment with omeprazole alone, neutrophil infiltration and H. pylori density decreased not only in the antrum but also in the corpus. There was no increase in intestinal metaplasia or mucosal atrophy as assessed endoscopically during follow-up. CONCLUSION: Changes in corpus gastritis in response to acid-suppressive therapy depend on the severity of gastritis before treatment. Long-term use of acid-suppressive therapy apparently does not accelerate the development of atrophy or intestinal metaplasia in Japanese patients.

Anti-Ulcer Agents↗

PubMed2000

Gastric acid secretion in dogs in response to combinations of beer, ethanol and peptone meal--the role of endogenous gastrin.

AIM: To examine the effects of beer, ethanol, peptone meal and combinations of either peptone meal and beer or peptone meal and ethanol on gastric acid secretion in vagally denervated pouch dogs. METHODS AND RESULTS: The oral administration of either 200 mL of beer, 5% ethanol or 10% peptone meal significantly stimulated gastric acid secretion for 60-90 min in these dogs. With 5% ethanol the plasma gastrin concentration was not affected for 90 min. Combinations of 10% peptone and beer (peptone-beer) or 10% peptone and 5% ethanol (peptone-ethanol) potentiated the acid secretion and increased the plasma gastrin level. While a selective cholecystokinin-B/gastrin receptor antagonist, S-0509, had no effect on ethanol-stimulated acid secretion, the compound markedly inhibited both peptone-beer-stimulated and peptone-ethanol-stimulated gastric acid secretion. Famotidine and atropine significantly inhibited gastric acid secretion stimulated by 5% ethanol, peptone-beer and peptone-ethanol. CONCLUSIONS: The mechanisms by which peptone-beer and peptone-ethanol stimulate gastric acid secretion may be mediated not only by increased plasma gastrin, but also by the action of histamine and acetylcholine coupled with the increased plasma gastrin. Ethanol-stimulated secretion appears to be unrelated to circulating gastrin, yet may be related to the acid regulatory mechanism involving histamine and acetylcholine.

Administration, Oral↗

PubMed2000

Ventricular energetics in Fontan circulation: evaluation with a theoretical model.

BACKGROUND: Both pulmonary and systemic circulation must be maintained by a single pump in Fontan circulation. This unique property of Fontan circulation may be related to decreased exercise tolerance or increased instantaneous postoperative mortality rate, often observed in patients with this circulation. To better understand Fontan physiology, the present study theoretically investigated cardiac performance of Fontan circulation by using ventricular-vascular coupling framework analysis. METHODS: End-systolic volume elastance (Ees), as a chamber contractile property, and effective arterial elastance (Ea), a lumped measure of ventricular afterload, were estimated both in normal left ventricular systemic circulation and in Fontan circulation. RESULTS: End-systolic volume elastance was decreased and Ea was increased in Fontan circulation. Both ventricular external stroke work (SW) and mechanical efficiency (EFF) under Fontan circulation were lower compared with those under normal circulation. Furthermore, the Ees-Ea relationship in Fontan circulation predicted limited cardiac reserve in terms of SW and EFF. Such cardiac performance in Fontan circulation stemmed from increased impedance due to the additional connection of the pulmonary vascular bed to the systemic vasculature and from the lack of a compensatory increase in contractility for increased afterload. CONCLUSIONS: Thus, it was inferred that Fontan circulation had intrinsic disadvantages and this may explain, in part, abnormal functional status and decline in survival following this procedure.

Blood Circulation↗

PubMed2000

Differentiation induction of canine osteosarcoma cell lines by retinoids.

The effect of two retinoids, all- trans and 9- cis retinoic acid, on the differentiation of three canine osteosarcoma cells (OOS, HOS, and POS) was examined using markers specifically expressed by phenotypic osteoblasts. Both retinoids induced morphologic differentiation in all the canine osteosarcoma cells. Retinoids enhanced cell flattening and spreading, as well as reduction in cell overlapping. Alkaline phosphatase (ALP) activity and ALP staining was enhanced in OOS, and HOS cells, but decreased in POS cells. These results may suggest that OOS and HOS cells have immature osteoblastic properties and POS cells have mature osteoblastic properties. Retinoids decreased osteocalcin production in all the osteosarcoma cells. They induced an increase in production of type I collagen in HOS and POS cells, but a decrease in OOS cells. These results indicate that retinoids induce differentiation of canine osteosarcoma cells, resulting in an altered expression of their malignant phenotype.

Alitretinoin↗