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Biomedical subjects

T Satoh

Publications and source records attributed to T Satoh.

At least 919 records · Page 51Linked to original sources

Regulation of squalene epoxidase in HepG2 cells.

Regulation of squalene epoxidase in the cholesterol biosynthetic pathway was studied in a human hepatoma cell line, HepG2 cells. Since the squalene epoxidase activity in cell homogenates was found to be stimulated by the addition of Triton X-100, enzyme activity was determined in the presence of this detergent. Incubation of HepG2 cells for 18 h with L-654,969, a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, increased squalene epoxidase activity dose-dependently. On the other hand, low density lipoprotein (LDL) and 25-hydroxy-cholesterol decreased the enzyme activity. These results demonstrate that squalene epoxidase is regulated by the concentrations of endogenous and exogenous sterols. The affinity of the enzyme for squalene was not changed by treatment with L-654,969. Cytosolic (S105) fractions, prepared from HepG2 cells treated with or without L-654,969, had no effect on microsomal squalene epoxidase activity of HepG2 cells, in contrast to the stimulating effect of S105 fractions from rat liver homogenate. Mevalonate, LDL, and oxysterol treatment abolished the effect of L-654,969. Simultaneous addition of cycloheximide and actinomycin D also prevented enzyme induction in HepG2 cells. From these results, the change in squalene epoxidase activity is thought to be caused by the change in the amount of enzyme protein. It is further suggested that squalene epoxidase activity is suppressed only by sterols, not by nonsterol derivative(s) of mevalonate, in contrast to the regulation of HMG-CoA reductase.

Binding, Competitive↗

Regulation of squalene epoxidase activity in rat liver.

Regulation of squalene epoxidase activity was examined in rat hepatic microsomes. The hepatic squalene epoxidase activity was high in the dark period and low in the light period. Three percent cholestyramine feeding increased the hepatic squalene epoxidase activity by 2.5-fold, and the administration of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, increased its activity by 2.1-fold. Co-administration of cholestyramine and lovastatin had a synergistic effect increasing the activity by 7.0-fold. On the other hand, cholesterol feeding reduced hepatic squalene epoxidase activity to 18%. The addition of sodium fluoride, a phosphatase inhibitor, and the treatment of the microsomes with ATP-Mg2+ had no effect on enzyme activity. HMG-CoA reductase activity has been reported to be regulated by cholesterol and unidentified metabolite(s) derived from mevalonate. However, since squalene epoxidase is less responsive than the reductase to the treatment with lovastatin, squalene epoxidase is thought to be regulated only by cholesterol pool.

Animals↗

[Clinical evaluation of cefuroxime axetil in acute dental infections. Double blind comparative study vs. cefaclor].

To evaluate objectively clinical efficacy, safety and usefulness of cefuroxime axetil (CXM-AX) in acute dental infections (periodontitis, pericoronitis and gnathitis), we carried out a comparison study using cefaclor (CCL) as the control. Both drugs were orally given after meals in a dose level of 250 mg (potency) t.i.d. for 3-7 days. 1. Clinical efficacy rates in all the treated cases were 81.6% (102/125) in the CXM-AX group and 82.5% (104/126) in the CCL group according to the assessment by physicians in charge, and 89.6% (112/125) and 83.3% (105/126), respectively, according to the assessment based on scores. No significant difference was found between the 2 treatment groups. In clinical efficacy (assessment by score) classified by background factors, efficacy rate in the CXM-AX group (90.6%, 58/64) was significantly higher (P less than 0.05) than that in the CCL group (75.0%, 48/64) in cases receiving no surgical treatment on the first day of drug administration. Other background factors than the above (no surgical treatment) factor or scores on the first day of drug administration, however, did not appear to influence clinical efficacies of 2 treatment groups. 2. As for the bacteriological response in all the treated cases, elimination rate in the CXM-AX group was 73.7% (28/38) and that in the CCL group, 78.3% (36/46), without significant difference between the 2 groups. 3. Regarding the safety, no significant difference was found between the 2 treatment groups. Adverse reactions were observed in 1 out of 128 cases (0.8%) in the CXM-AX group and 6 out of 132 cases (4.5%) in the CCL group. Abnormal laboratory test values were noted in 8 out of 86 cases (9.3%) in the CXM-AX group and 5 out of 91 cases (5.5%) in the CCL group. None of these differences between 2 treatment groups was statistically significant. 4. Usefulness rates in all the treated cases were 81.6% (102/125) in the CXM-AX group and 81.7% (103/126) in the CCL group, thus significant difference was observed between the 2 groups. From the above results, CXM-AX is considered to be a useful drug like CCL in the treatment of acute dental infections.

Acute Disease↗

Chemical synthesis of the 5'-terminal structure of U1 RNA.

A new method for the synthesis of N2,N2-dimethylguanosine (DMG) is developed by reductive C-S bond cleavage by use of tributyltin hydride. An improved method for the synthesis of the key intermediate (1) for construction of the 5'-terminal structure of U1 RNA, which has a trimethylated cap (TMG) structure at its 5' end, is also described. By the use of 1, several TMG-capped ribonucleosides and oligonucleotides were synthesized.

Guanosine↗

[The effect of cepharanthin on adjuvant chemotherapy induced bone marrow suppression in patients with breast cancer].

We studied the effect of Cepharanthin on bone marrow suppression induced by adjuvant chemotherapy in primary breast cancer patients in our hospital. The 36 patients with breast cancer were divided into two groups. Both groups were administered of MMC 20 mg intravenously on the day of radical operation. One group (23 patients) was administered of Cepharanthin 60 mg every day, but the other (13 patients) group was not administered. In the leukocyte count at 3 weeks after post operation, 82.6% (19 out of 23) of the patients who were administered cepharanthin kept more than 70% of pre-operation's leukocyte. On the other hand, only 46.1% (6 out of 13) of the patients who were not administered Cepharanthin kept more than 70% of pre-operation's leukocyte. The number of thrombocyte was not decreased in both groups. Side effects by Cepharanthin were not observed in this study.

Alkaloids↗

New cavity forms in first deciduous molars which maximize dentin thickness between cavity and pulp chamber.

Using a total of 60 human extracted first deciduous molars (30 upper molars and 30 lower molars), we contrived a variety of ideal cavities having dentin thicknesses below the cavity (subcavitary dentin) that measure approximately 1 mm in thickness from the pulp chamber at any point of measurement and also having a retentional groove prepared in such a way that detachment of a filling material is prevented. The transparent specimens prepared from the cavity-containing teeth were cut into serial sections of 93 microns. These sections were reconstructed using a personal computer. The thickness of dentin below the cavity was measured in randomly selected sections. Results obtained were as follows: 1. An ideal thickness of the subcavitary dentin was preserved for upper first deciduous molar by preparing a retentional groove lingually or by providing a dovetail-like shape to mesio-distolingual sides in the cavity; for lower first deciduous molar, any form of cavitation worked. 2. In the upper first deciduous molars, the margins of the cavity were displaced medially to the summits of the respective cusps 1.9 mm at the buccal side and 1.2 mm at the lingual side. In the lower first deciduous molars, the buccal margin medially measured 0.9 mm and the lingual margin measured 0.6 mm at the mesial side. At the distal side, the buccal and lingual margins measured 1.2 mm and 1.0 mm, respectively. 3. The ratio of cavity width to the distance between the summits of the buccal and lingual cusps was 1/3 in upper deciduous first molars and 2/5 in the lower first deciduous molars. 4. In the upper first deciduous molars, the depths of the buccal and lingual walls of the cavity at the center of the central groove were both 1.1 mm. In the lower first deciduous molars, the cavity formed with its center at the middle of the transverse ridge had a depth of 1.5 mm at the buccal wall and a depth of 1.7 mm at the lingual wall. The cavity formed with its center at the central fossa had a depth of 1.2 mm at the buccal wall and 1.1 mm at the lingual wall. 5. The width of the gingival wall in the proximal box measured 0.6-0.7 mm in upper and lower first deciduous molars.

Child↗

[Comparison of two-dimensional echocardiography and Tl-201 SPECT in the evaluation of ischemic heart disease].

To ascertain the influence of severity of coronary stenosis and the presence or absence of collateral circulations on echocardiographic (2DE) asynergy or abnormal myocardial perfusion by exercise Tl-201 SPECT, we performed a correlative study of 40 patients undergoing coronary angiography, including 27 with myocardial infarction and 13 with angina pectoris, whose mean age was 55 years. Each view of the left ventricle (LV) obtained by both methods was assigned to five segments; i.e., anterior, septal, inferior, lateral and apical. The correlation of abnormal segments was investigated using both methods. The segments showing a severe perfusion defect coincided those with severe asynergy. Among 116 segments with normal perfusion, 99 (85%) revealed normal wall motion, but the remaining 15% showed asynergy. Among 84 segments with abnormal myocardial perfusion, 26 (31%) had normal wall motion, and most of these were non-infarcted regions. Concerning the severity of coronary artery stenosis, greater than 99% coronary arterial stenoses existed in most of the segments showing a complete defect or incomplete redistribution on Tl-201 SPECT and akinesis or hypokinesis on 2DE. Collaterals were observed in 22% of the segments with a complete defect and 66% of segments with incomplete redistribution; whereas, there was no significant correlation between the severity of LV wall motion abnormality and the presence or absence of collaterals. The severity of asynergy is possibly related to the severity of abnormal myocardial perfusion, however, asynergy could occur at the site of ischemic regions where Tl-201 SPECT can not detect the abnormalities. In patients with myocardial infarction who show incomplete redistribution by exercise Tl-201 SPECT, temporal ischemia of collaterals might cause such a perfusion abnormality.

Adult↗

New cavity forms in second deciduous molars which maximize dentin thickness between cavity and pulp chamber.

This study was designed to devise configuratively ideal cavity formations using 49 second deciduous molars, consisting of 25 extracted from the maxilla and 24 from the mandible. A cavity having at least 1 mm subcavitary (below the cavity) dentin thickness at any point of measurement and having an appropriately formed and positioned retention was defined as an ideal cavity. The same methods were used as in our previous study of first deciduous molars. The following results were obtained: 1. In upper second deciduous molars, the subcavitary dentin thickness was thin at the mesiobuccal side of the cavity; it measured 0.9 mm. In lower second deciduous molars, the subcavitary dentin thickness was thin at the mesiobuccal, distolingual sides of the cavity, and central fossa, where the retentional groove was provided; it measured 0.8-0.9 mm. The other measured values exceeded 1.0 mm. All thickness measurements were very close to the values considered as ideal. 2. In upper second deciduous molars, the margins of the cavity were positioned medially to the summits of respective cusps, 1.8-2.0 mm at the buccal side and 1.5 mm at the lingual side. The entire cavity was located lingually. 3. In lower second deciduous molars, the buccal margin of the cavity was positioned 1.7 mm medially to the summit of the distobuccal cusp and 1.2-1.3 mm medially to the summits of the other buccal cusps. The lingual margin was positioned 1.4-1.5 mm medially to the summits of respective cusps. medially to the summits of respective cusps. 4. The buccolingual width of the cavity amounted to 1/3 of the distance between the summits of the buccal and lingual cusps in both upper and lower second deciduous molars. 5. At the mesial side, the depth of cavity was 1.4 mm at the buccal wall and 1.5 mm at the lingual wall in upper second deciduous molars, and 1.4 mm at the buccal wall and 1.6 mm at the lingual wall in lower second deciduous molars. 6. The width of gingival wall in the proximal box measured 1.0 mm in both upper and lower second deciduous molars.

Child↗

[Studies on suppurative lesion and bone distribution of peroral antimicrobial agents (LAPC and TFLX) to experimental infected rabbits].

The models of infection in the rabbits mandible using Streptococcus milleri and Bacteroides fragilis by the method of Satoh-Heimdahl were prepared. A penicillic peroral antimicrobial agent, lenamipicillin (LAPC), and pyridone carboxylic acid peroral antimicrobial agent, tosufloxacin tosilate (TFLX), were administered to infected and healthy groups. Drug concentrations in the serum, pus, mandible, maxilla, humerus, sternum, costa, ilium, femur, tibia, liver, and kidney were determined by a biological method. The data were submitted to pharmacodynamic analysis and compared. The following results were obtained. The concentration of LAPC in the serum and various bone tissues was 1.2-6.4 times higher in the infected group than in the healthy group. The concentration of TFLX in the serum and bone tissues was 1.1-3.7 times higher in the infected group than in the healthy group. Moreover, concentrations in the liver 1.1-fold and 2.1-fold higher in the infectious group than in the healthy group in the LAPC and TFLX administration groups, respectively, and 1.1-fold and 1.3-fold higher in the kidney in the LAPC and TFLX groups, respectively. Both LAPC and TFLX diffused to the pus more satisfactorily than to the serum. The Cmax ratios of pus to infected serum were 1.48 and 1.81 for LAPC and TFLX, respectively, and the AUC ratios of pus to infected serum were 1.31 and 1.62 in LAPC and TFLX, respectively. These results indicated that both LAPC and TFLX are distributed satisfactorily to the local foci in the mandible, and that their systemic diffusion exerted immediate clinical effects.

4-Quinolones↗

[Studies on bone and suppurative lesion distribution of antimicrobial suppositories (Ampicillin and Ceftizoxime) to experimental infected rabbits].

The investigation has been made regarding transfer of the antimicrobial agents into the osseous tissues in rabbit and into the mandibula in experimental infected rabbit model by making intrarectal administration of ampicillin (ABPC) and ceftizoxime (CZX). The preparation of the infected model were made according to the procedure of Satoh and Heimdahl. Pharmacokinetic analysis was made by measuring concentration of these antimicrobial suppositories transferred according to the biological measuring method in serum, mandibula, maxilla, ilium, tibia, sternum, liver and pus. The results were as follows: 1) In the infected group given ABPC, the concentration of the drug in mandibula and maxilla were approx. 21.5-52.9% of those in serum. 2) In the normal healthy group given ABPC, their concentration in tissues were approx. 13.9-23.7% of those in serum. 3) In the infected group given CZX, their concentration in pus and osseous tissues were approx. 12.7-61.8%. 4) In the normal healthy group given CZX, their concentration in osseous tissues were approx. 12.4-22.9% of those in serum. 5) In a comparison made between the infected and normal healthy group, transfer of the drugs into the infected group were observed in higher rates in serum and all osseous tissues. 6) The serum concentration of the antimicrobial suppositories (ABPC and CZX) by intrarectal administration showed transfer in far higher rate than those by oral administration and exhibited transfer of concentration at its peak equal to that by intramuscular administration.

Ampicillin↗

Effect of the H-2 and Igh complexes on the susceptibility to ultraviolet B-induced immunosuppression in murine contact sensitivity and contact photosensitivity.

We examined the genetic control of ultraviolet B (UVB)-induced immunosuppression in contact sensitivity (CS) to DNFB, picryl chloride, and oxazolone, and contact photosensitivity (CPS) to TCSA by using various H-2- and Igh-congenic strains. The CPS responses were inhibited by UVB preirradiation in all strains tested except for A/J mice, whereas only certain strains showed the immunosuppressive effect of UVB on the CS responses. In C.B-20 (H-2d, Igh-VbCb) and C3H (H-2k, Igh-VjCj) mice, the responses to 2-3 contact agents were suppressed by UVB pre-exposure. In C.AL-20 (H-2d, Igh-VdCd) mice, the UVB-induced suppression was observed in only 1 of the 3 CS systems. In contrast, BALB/c (H-2d, Igh-VaCa), BALB.B (H-2b, Igh-VaCa), BAB-14 (H-2d, Igh-VaCb), DBA/2 (H-2d, Igh-VcCc) and A/J (H-2a, Igh-VeCe) mice did not show immunosuppression in these CS systems. These data suggested that the susceptibility to UVB in the induction of cutaneous sensitivity depended on the mouse strain. There was no significant association between the susceptibility to UVB and the H-2 haplotype. However, the Igh complex partially contributed to UVB-induced suppression, as observed in a comparison of the CS responses between the Igh congenic strains, BALB/c, BAB-14 and C.B-20.

Animals↗

Karyometric and DNA content analyses of cancer cells in stage III breast cancer with reference to prognosis.

Karyometric and DNA content analyses were simultaneously performed on 32 cases of stage III invasive ductal breast cancer using an image analysis system. From the karyometric analysis, the nuclear areas (NAs; microns 2) were (mean +/- SD) 36.27 +/- 9.40 in five-year survivors (n 17) and 57.14 +/- 13.26 in non-survivors (n 15). The nuclear shape factors (NSFs; NSF = 4 pi X NA/NP2; NP, nuclear perimeter) were 0.756 +/- 0.037 in survivors and 0.716 +/- 0.040 in non-survivors. The NA was significantly larger (P less than 0.01) and the NSF significantly lower (P less than 0.01) in non-survivors than in survivors. From the DNA content analysis, the DNA content values (c; see Measurements section) were +/- 2.59 +/- 0.70 in survivors and 3.72 +/- 1.08 in non-survivors. The percentages of aneuploid cells over 4c were 7.10 +/- 9.89 in survivors and 23.07 +/- 20.19 in non-survivors. The DNA content and the percentage of aneuploid cells over 4c were significantly higher (P less than 0.01) in non-survivors than in survivors. This method may be valuable for estimating the prognosis of patients with invasive ductal carcinoma of the breast.

Adult↗

Comparisons of heptaminol AMP amidate and dibutyryl cyclic AMP on murine splenocytes proliferation.

Hepataminol AMP amidate (HAA), a nucleotide derivative possessing immunopotentiating activities, inhibited the mitogen-induced proliferation of murine splenocytes in vitro at the higher concentrations. Concanavalin A-induced mitogenic response was inhibited to 65 and 15% of the control value by HAA at the concentrations of 10(-4) and 10(-3) M, respectively. HAA also inhibited phytohemagglutinin P and lipopolysaccharide-induced responses at the same concentrations. The pattern of inhibition of mitogen-induced responses by HAA at higher concentrations was found to be almost similar to that of dibutyryl cyclic AMP (DbcAMP). Both HAA and DbcAMP also inhibited the blastogenesis of spleen cells in one way mixed lymphocyte reaction.

Adenosine Monophosphate↗

[A case of multiple tumors].

A 54-year-old man was admitted to our clinic for a further examination of rectal and liver tumors, after which a rectal cancer, a hepatocellular carcinoma (HCC), a hemangioma of the liver a retroperitoneal cyst, and a submucosal tumor of the stomach (SMT) were diagnosed by means of a colonoscopy, a gastroscopy, and US, CT, and angiography, these tests also revealing elevated CEA and AFP levels. A hepatic subsegmentectomy and a Miles's operation, as well as an enucleation of other liver tumors and an SMT, were performed and a retroperitoneal cyst was removed. The histopathological finding of the rectal cancer was a moderately differentiated adenocarcinoma, while the liver tumors were determined as being an HCC of the trabecular type, adenomatas revealing hyperplasia, a hemangioma, and the SMT showing a benign leiomyoblastoma.

Adenocarcinoma↗

[Treatment of acute lymphoblastic leukemia in adults by the modified protocol of L-10M (Sloan-Kettering)].

We have treated 20 adult patients with acute lymphoblastic leukemia (ALL) and 2 patients with lymphoblastic lymphoma with a protocol modified from L-10M of the Memorial Sloan Kettering Cancer Center. Eighteen patients (81.8%) entered complete remission (CR). Eight of them eventually relapsed (only 1 patient had a meningeal relapse) and died. Median CR duration was 19 months (median overall follow-up of 35 months and 50% remission duration was not yet determined. Median overall survival was 19 months. Three patients died of sepsis during remission induction, but all of other deaths were due to resistant or relapsed leukemia. The four patients who completed 3.5 year's modified L-10M protocol were free from relapse for 6-11 months (mean 8.7). Although further follow-up is necessary, we suggest that modified L-10M protocol is effective for adult ALL and long-term survival may be available.

Adolescent↗