Biomedical subjects

S Fukushima

Publications and source records attributed to S Fukushima.

At least 37 records · Page 2Linked to original sources

PubMed2001

Possible prevention by abieslactone of development of diethylnitrosamine-initiated GST-P positive foci in the rat liver.

Triterpenoid compounds, isolated from plants of Abies genus (Pinceae), are known to exert anti-tumor promotion activities in mouse skin carcinogenesis. In the present study, we investigated whether AVB-1 and acid and acid methyl ester derivatives have inhibitory effects on rat hepatocarcinogenesis by using a liver medium-term bioassay for carcinogens (Ito's test), immunohistochemically assessing the numbers and areas per cm(2) of preneoplastic lesions, glutathione S-transferase placental form (GST-P)-positive foci. In experiment 1, 6-week-old male Fisher 344 rats were given a single intraperitoneal injection of diethylnitrosamine (200 mg/kg b.w.) and subjected to two-thirds partial hepatectomy at week 3. From weeks 2 to 8, the compounds were given three times a week at a dose of 1 mg/kg b.w. by i.g. gavage and found to significantly decrease the number of GST-P-positive foci in the liver. In experiment 2, AVB-1 was given three times a week at doses of 3, 1, or 0.3 mg/kg b.w. by i.g. gavage from weeks 2 to 8. All doses of AVB-1 significantly decreased the numbers of GST-P-positive foci. Thus, our results suggest that AVB-1 is a chemopreventive agent for rat hepatocarcinogenesis.

Alkylating Agents↗

PubMed2001

Promotion of chemically induced rat esophageal tumorigenesis with post-initiation ethanol modification.

Post-initiation ethanol modification on N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal carcinogenesis model was investigated in male, 6-week-old, F344 rats that received s.c. injections, 3 times per week, of 0.5 mg/kg NMBA for the first 5 weeks and then were treated with 0% (Group 1), 3.3% (Group 2), and 10% (Group 3) ethanol in the drinking water for up to 20 weeks. Group 4 received 10% ethanol without NMBA administration and Group 5 was maintained without any chemical treatment. There were no statistical differences in the incidence and multiplicity of esophageal tumors among Groups 1 to 3. However, the multiplicity of hyperplasias was statistically greater in Group 3 than in Groups 1 or 2. Esophageal epithelia of all rats in Groups 4 and 5 demonstrated a normal histology. BrdU labelling indices of tumors and hyperplasias in NMBA-treated groups were essentially similar, although cycline D1 was overexpressed to a greater extent in tumors and also hyperplasias of Group 3 than in Groups 1 or 2. The results indicated ethanol to exert weak promotion effects through cycline D1 overexpression on rat esophageal tumorigenesis initiated with NMBA.

Animals↗

PubMed2001

Merits and demerits of operative procedure to the trachea in patients with differentiated thyroid cancer.

Local radical thyroidectomy, including cervical lymph node dissection and combined circumferential resection of the trachea, has been performed over the past 20 years in 31 patients with differentiated cancer invading the trachea. The 5- and 10-year survival rates for these patients were 77.4% and 66.7%, respectively. In 19 of the 31 (61%) cases the recurrent nerve was resected because of direct cancer invasion. Bilateral recurrent nerve palsy occurred in 12 patients, 3 of whom were managed postoperatively using a T-shaped tube for preservation of the larynx. Hoarseness remained in 21 patients. In two patients with recurrent cancer invasion of the larynx, partial laryngectomy and hemilaryngectomy were performed, and reconstruction was done using ear cartilage without postoperative dyspnea or dysphagia. Parathyroid function is an important factor in regard to the quality of life of patients. In 22 patients at least one of the parathyroids was preserved. Postoperative calcium administration was necessary in 14 patients. Our long-term observations indicate that local radical thyroidectomy with combined resection of the trachea can serve as a useful treatment for advanced differentiated cancer invading the airway.

Adult↗

PubMed2001

Renal pelvic carcinoma producing granulocyte colony-stimulating factor: report of a case.

A 69-year-old man was admitted to our hospital because of anorexia and weight loss. Abdominal computed tomography showed an irregularly contoured mass in his left renal pelvis. The patient had a remarkable degree of leukocytosis with no obvious focus of infection. An enzyme immunoassay of the serum revealed a remarkably high concentration of granulocyte colony-stimulating factor (G-CSF). The patient died 6 weeks after admission without a resection of the renal pelvic tumor. At autopsy, the tumor involved the pancreas, stomach, and descending colon. The histopathologic diagnosis was squamous cell carcinoma with sarcomatous change. Immunohistochemical staining using anti-G-CSF antibody demonstrated immunoreactivity in the cancer cells. To our knowledge, this is the first case of renal pelvic carcinoma proven to produce G-CSF reported in English.

Aged↗

PubMed2001

Augmentation of megakaryocytopoiesis within the hematopoietic microenvironment of human granulocyte colony-stimulating factor transgenic mice.

OBJECTIVE: Megakaryocytopoiesis was dramatically augmented in human granulocyte colony-stimulating factor transgenic mice (G-Tg) compared to littermates. We examined the characteristics of megakaryocytes and megakaryocyte progenitor cells in these mice. MATERIALS AND METHODS: The numbers of colony-forming unit megakaryocytes (CFU-MK) and megakaryocytes in hematopoietic organs were counted. The megakaryocytes of G-Tg were examined ultrastructurally, and bone marrow transplantation studies using congenic G-Tg (Ly5.2) and C57BL/6 (Ly5.1) were performed. The number of day-14 colony-forming unit spleen (CFU-S) that contained megakaryocytes in [Ly5.1 > G-Tg] and [G-Tg > Ly5.1] mice also was counted. RESULTS: The number of CFU-MK increased markedly in the spleen, bone marrow, and peripheral blood. The number of megakaryocytes in the spleen and bone marrow also were increased in G-Tg mice. Ultrastructural analyses revealed that megakaryocytes in G-Tg mice were immature. Bone marrow transplantation studies of [Ly5.1 > G-Tg] mice resulted in a significantly increased number of megakaryocytes compared to [G-Tg > Ly5.1] mice. The number of day-14 CFU-S that contained megakaryocytes was increased markedly in [Ly5.1 > G-Tg] mice compared to [G-Tg > Ly5.1] mice. In vitro differentiation of megakaryocytes in [Ly5.1 > G-Tg] mice was induced by interleukin-11 and thrombopoietin. CONCLUSION: The results showed that the hematopoietic marrow microenvironment of G-Tg is important in augmenting megakaryocytopoiesis. [Ly5.1 > G-Tg] mice are potentially useful as a source of murine megakaryocytes and their progenitors.

Animals↗

PubMed2001

Biventricular repair in a patient having double outlet right ventricle with unusual straddling of the mitral valve.

The authors achieved biventricular repair in a 1-year-old boy having double outlet right ventricle and unusual straddling of the mitral valve. There was a substantial abnormal muscular bar present within the right ventricle, and some of the tendinous cords of the mitral valve were attached to this structure. Preoperative echocardiography was particularly informative in enabling the surgeon to arrange the optional operative procedures. The postoperative course was smooth and uneventful.

Double Outlet Right Ventricle↗

PubMed2001

Are tobacco use and urine pH indicated as risk factors for bladder carcinoma?

BACKGROUND: Many case-control and cohort studies have shown a positive relationship between bladder carcinoma and tobacco use. Recently, urine pH has been reported to influence aromatic amine carcinogenesis, which have been implicated as potent carcinogens in bladder carcinoma patients. Herein the correlation between bladder carcinoma, tobacco use and urine pH is reported. METHOD: One hundred and forty-one patients with bladder carcinoma and 128 patients with benign prostatic hyperplasia or urolithiasis as controls were selected. All patients were admitted to Osaka City University Hospital for the purpose of surgical treatment. Urine pH was checked by a test tape. RESULTS: Of the patients with bladder carcinoma, 106 were smokers and 35 were non-smokers. In contrast, the number of smokers in the control group was 76 and that of non-smokers was 52. The odds ratio in the bladder carcinoma group calculated for the smoker patients was 2.07, showing a significant correlation between bladder carcinoma and tobacco use. Regarding urine pH, acidic urine was found in 126 patients in the bladder carcinoma group and in 116 patients in the control group. The odds ratio in the bladder carcinoma group for acidic urine was 0.87, showing no significant relationship between bladder carcinoma and urine pH. CONCLUSION: The study found a positive relationship between bladder carcinoma and tobacco use; however, it could not establish a clear relationship between bladder carcinoma and urine pH, even in the smoker group.

Aged↗

PubMed2001

Clinical application of intraoperative measurement of choline acetyltransferase activity during functioning free muscle transfer.

Intraoperative measurement of choline acetyltransferase (CAT) activity was used for evaluation of the functional status of donor nerves during functioning free muscle transfer (FFMT). Twelve patients underwent the procedure. Seven patients had a brachial plexus injury, 3 Volkmann's contracture, 1 chronic peroneal nerve injury, and 1 forearm extensor muscle loss after wide resection of soft tissue sarcoma. The purpose of reconstruction using FFMT was to achieve wrist extension in 4 patients, simultaneous elbow flexion and finger extension in 3, elbow flexion in 2, finger extension in 1, finger flexion in 1, and ankle extension in 1 patient. The gracilis muscle was transferred in all cases. The donor nerves for FFMT that were evaluated by CAT activity included 5 spinal accessory nerves, 4 posterior interosseous nerves, 2 anterior interosseous nerves, and 1 deep peroneal nerve. Fascicles with greater than 2,000 cpm CAT activity were considered to reliable and used as donor motor nerves. All muscles had reinnervation by 3.2 months (range, 2-5 months) and obtained useful recovery. Intraoperative measurement of CAT activity can provide direct and quantitative information about the functional status of donor nerves during FFMT.

Adolescent↗

PubMed2001

Assessment of newly developed perfluorocarbon emulsion: oxygen carrying capacity as the blood substitute in vivo.

This study provides the evaluation of oxygen carrying capacity of the novel perfluorocarbon emulsion (Neo-PFC) produced by the new emulsifying technology named High Pressure Process. For the performance comparison of oxygen carrying abilities of Neo-PFC and a representative PFC emulsion, the oxidation states of cerebral tissues in substituted animals were measured by near-infrared spectrometry. After the 70% exchange transfusion of whole blood of rats by Neo-PFC and Fluosol-DA, fractional inspired oxygen (FiO2) was gradually decreased from 100% to 0%. As the control experiments, the blood was substituted by Krebs Ringer bicarbonate buffer containing 3% BSA. When the blood of rats was substituted by Neo-PFC, Cyt. ox., a terminal enzyme in mitochondrial respiratory chain maintained fully oxidized state with FiO2 values between 100 to 40%. By contrast, in the models substituted by Fluosol-DA and BSA-buffer. Cyt. ox. was gradually reduced with FiO2 values below 60% and 80%, respectively. This specific advantage of Neo-PFC was explained by its higher oxygen solubility in arterial blood. The novel PFC emulsion prepared by the new emulsifying technology is a potential basis for blood substitutes.

Animals↗

PubMed2001

Interleukin-11 induces osteoblast differentiation and acts synergistically with bone morphogenetic protein-2 in C3H10T1/2 cells.

Interleukin-11 (IL-11) is a pleiotropic cytokine that supports various types of hematopoietic cell growth and is involved in bone resorption. We report here the involvement of recombinant human IL-11 (rHuIL-11) in osteoblast differentiation in mouse mesenchymal progenitor cells, C3H10T1/2. rHuIL-11 alone increased alkaline phosphatase (ALP) activity and upregulated expression levels of osteocalcin (OC), bone sialo protein (BSP), and parathyroid hormone receptor (PTHR) mRNA. rHuIL-11 had no effect on expression of type II collagen, peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), adipocyte fatty acid-binding protein P2 (aP2), and myogenic MyoD protein (MyoD). Recombinant human bone morphogenetic protein (rHuBMP)-2 increased ALP activity and mRNA expression of these genes except for MyoD. The expression patterns of ALP activity and osteoblast-specific or chondrocyte-specific genes suggest that rHuIL-11 may be involved in early differentiation of osteoblasts at a step earlier than that which is affected by rHuBMP-2. In support of this hypothesis, combined treatment with rHuIL-11 and rHuBMP-2 synergistically increased ALP activity and mRNA expression of OC and type II collagen, rHuIL-11 also abrogated the increased levels of PPAR-gamma2, aP2 mRNA caused by rHuBMP-2. Our results suggest that rHuIL-11 alone and in combination with rHuBMP-2 can induce osteoblastic differentiation of progenitor cells and plays an important role in osteogenesis.

Alkaline Phosphatase↗

PubMed2001

Treated natural history of superficial bladder cancer.

BACKGROUND: The present study was conducted to examine the natural history of superficial bladder cancer. METHODS: One hundred and forty-four patients with superficial bladder cancer who had been treated with transurethral resection of bladder tumor (TURBt) alone were analyzed. RESULTS: The non-recurrence rate was 64.8% at 36 months and 61.2% at 60 months after TURBt. When the non-recurrence rate after TURBt was analyzed by background variables, the rate differed significantly between the solitary tumor group and the multiple tumor group. The tumor recurrence hazard curves for the entire population had one high peak before 500 days and another slight peak around 1500 days after TURBt. CONCLUSIONS: These results will provide basic information useful when evaluating new regimens of intravesical instillation therapy for prophylaxis of superficial bladder cancer after our complete TURBt in the Nara Uro-Oncology Research Group.

Aged↗

PubMed2001

Suppression of chemical carcinogenesis by water-soluble organosulfur compounds.

The chemopreventive effects of five water-soluble organosulfur compounds, S-methylcysteine (SMC) and four analogs, were examined on the promotion stage of diethylnitrosamine hepatocarcinogenesis in male F344 rats, using the medium-term bioassay (Ito test), which is based on the two-step model of hepatocarcinogenesis. In addition, we investigated the modifying effects of SMC and cysteine on the initiation stage of rat hepatocarcinogenesis. Carcinogenic potential was scored by comparing the numbers and areas of a putative neoplastic lesion, glutathione S-transferase placental form (GST-P)--positive hepatocellular foci. SMC and cysteine significantly decreased the number and area of GST-P--positive foci when given in the promotion stage of the Ito test. When given during the initiation stage, these two organosulfur compounds also significantly inhibited focus formation. Liver ornithine decarboxylase activity after two thirds partial hepatectomy and the proportion of hepatocytes positive for proliferating cell nuclear antigen significantly decreased the number of aberrant crypt foci in the colon in a multiorgan carcinogenesis bioassay of rats. These results support SMC and cysteine as chemopreventive agents for hepatocarcinogenesis and colon carcinogenesis. Their intake may be of importance for cancer.

Animals↗

PubMed2001

Lack of change in the levels of liver and kidney cytochrome P-450 isozymes in p53+/- knockout mice treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

We have previously shown that p53(+/-) knockout mice are highly sensitive to urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in spite of a lack of effects of p53 heterozygosity on N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN) excretion in urine. To determine the influence of p53 deficiency on in vitro formation of BCPN, mutagenicity of BBN and BCPN and levels of several cytochrome P450 (CYP) isozymes, groups of five p53(+/-) knockout and wild-type mice (littermates), as well as animals of the C57BL/6 parental strain, were administered 0.025% BBN in their drinking water for 4 weeks. The livers and kidneys were then used for analyses of BBN metabolism, western immunoblotting and Ames liquid incubation. BBN treatment caused a slight decrease in BCPN formation in the livers of C57BL/6 mice, but there was no significant difference between p53 knockout, wild-type and C57BL/6 mice. In kidney BCPN formation in p53 knockout mice was 33-46% less than that in their wild-type counterparts. Using anti-rat CYP antibodies, CYP1A2, 2B9/10, 2E1 and 3A11/13 were constitutively detected in liver microsomes and CYP2E1 and 3A11/13 in the kidney. Densitometric determination of these CYP proteins revealed no significant variation in levels detected in both tissues among the four groups of mice. BBN and BCPN were not mutagenic for Salmonella typhimurium TA100 in either the absence or presence of liver S9 from untreated mice and rats and from p53 knockout mice treated with BBN. In conclusion, p53 deficiency and BBN had no enhancing effects on metabolism of BBN to BCPN and expression of the CYP isozymes typically responsible for activation of environmental carcinogens, including both of the N-nitrosamines tested, and their mutagenicity, indicating that the high susceptibility of p53(+/-) knockout mice is not attributable to metabolic activation in liver and kidney by CYP isozymes or urinary excretion of BCPN.

Animals↗

PubMed2001

Antitumor activity, optimum administration method and pharmacokinetics of 13,14-dihydro-15-deoxy-deoxy-Delta7 -prostaglandin A1 methyl ester (TEI-9826) integrated in lipid microspheres (Lipo TEI-9826).

13,14-Dihydro-15-deoxy-Delta7-prostaglandin A1 methyl ester (TEI-9826), an antitumor prostaglandin analog, is a candidate for clinical trial. In the present study, we examined its biological stability in vitro, antitumor activity in vitro and in vivo, and pharmacokinetics. Although TEI-9826 was rapidly hydrolyzed to the carboxylic acid form (TOK-4528), TOK-4528 as well as Delta12-prostaglandin J2 (PGJ2) were found to be stable in rat, mouse and human serum in vitro. TEI-9826 exhibited nearly identical or greater potential antitumor activity compared to Delta12-PGJ2 and Delta7-PGA1 in vitro against Colon26 tumor cells. Further evaluation of TEI-9826 using the 38 human cancer cell lines panel and COMPARE analysis suggested that its mode of action is quite different from other anticancer agents that are currently used. TEI-9826 was integrated into lipid microspheres (Lipo TEI-9826) for dosing. Growth inhibition by Lipo TEI-9826 against Colon26 tumor inoculated s.c. in mice depended on administration route, i.e. at 80 mg/kg, no growth suppressive effect was observed for daily bolus i.v., but significant growth suppressive effect was observed for daily i.p., daily s.c. every other day s.c. and 4 times a day continuous (5 min) i.v. These tumor growth-suppressive effects were cytostatic and the tumor started to regrow at the end or a few days after the end of administration. The pharmacokinetic study suggested that maintaining the blood level of TEI-9826 and/or TOK-4528 was essential for their antitumor effects. These results show that continuous i.v. infusion might be the most suitable administration method of Lipo TEI-9826 for clinical trial.

Animals↗

PubMed2001

p53 and H-ras mutations and microsatellite instability in renal pelvic carcinomas of NON / Shi mice treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine: different genetic alteration from urinary bladder carcinoma.

We previously reported p53 mutations to be frequent (greater than 70%), whereas both H-ras mutations and microsatellite instability (MSI) were infrequent (about 10%), in urinary bladder carcinomas (UBCs) and their metastatic foci in the N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced mouse urothelial carcinogenesis model. In the present study, an analysis of p53 and H-ras mutations as well as MSI was performed on 12 renal pelvic carcinomas (RPCs) and 8 metastatic or invading foci produced by the same experimental procedure. Histologically, 10 of the RPCs were transitional cell carcinomas and the remaining 2 were squamous cell carcinomas. p53 mutations were infrequent and only found in one primary RPC (8%), its metastatic foci and an invading lesion in another animal (in a total 2 of 12; 17%). H-ras mutations were slightly more frequent (found in 3 of 12 animals; 25%), 4 of 5 involving codon 44, GTG to GCG, not a hot-spot reported for human cancers. In two cases, H-ras mutations were confined to lung metastasis and not detectable in their primary RPCs. MSI analysis was available for 6 pairs of primary RPCs and their metastatic foci, and 4 animals (67%) had MSI at one or more microsatellite loci. Overall, the distribution of genetic alterations differed from that in UBCs produced by the same experimental protocol. The results thus suggest that different genetic pathways may participate in carcinogenesis of the upper and lower urinary tract due to BBN.

Animals↗

PubMed2001

Transdermal drug delivery by electroporation applied on the stratum corneum of rat using stamp-type electrode and frog-type electrode in vitro.

Transdermal enhancement effects of electroporation applied only on the stratum corneum by two electrode types, the stamp-type electrode and the frog-type electrode, were investigated in vitro using excised rat skin. Carboxyfluorescein (CF) was selected as a model compound. The excised skin was set in a Franz type diffusion cell and a square wave electric pulse was applied to the stratum corneum under various electric pulse conditions. We determined the permeability of CF to the receptor compartment under these conditions. Voltage, electric pulse length, and number of electric pulses, were varied from 10 to 1000 V, 50 micros to 15 ms and 5 to 30 pulses, respectively. Flux rate was enhanced as the electric pulse condition strengthened. However, the maximum value was attained in the flux rate, above which no increase was observed despite strengthening of the electric pulse. Although at low electric pulses, the enhancement effect of the frog-type electrode was superior to that of the stamp-type electrode, the maximum flux rates were the same. These results indicate that electroporation on the stratum corneum using the stamp-type electrode or frog-type electrode, is useful for transdermal drug delivery.

Administration, Cutaneous↗

PubMed2001

Inhibition by ginseng of colon carcinogenesis in rats.

The inhibitory effects of ginseng on the development of 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in the colon were investigated in rats. Male, 6-week-old rats were injected with DMH once a week for 4 weeks. Rats in Groups 1 and 2 were fed diets containing red and white ginseng, respectively, at a dose of 1% for 5 weeks, starting one week before the first treatment of DMH. Animals in Groups 3 and 4 received red or white ginseng for 8 weeks starting after DMH treatment. Group 5 served as a carcinogen control group. Numbers of ACF with at least four crypts were significantly reduced in the colon of Group 2 treated with red ginseng combined with DMH. Moreover, rats were injected with DMH 4 times at one-week intervals. They were also fed diets containing 1% red or white ginseng or the control diet throughout 30 days of the experiment. Treatment with red ginseng resulted in a significant decrease of 5- bromo-2'-deoxyuridine labeling indices in colonic crypts comprising ACF. These findings suggest that dietary administration of red ginseng in combination with DMH suppresses colon carcinogenesis in rats, and the inhibition may be associated, in part, with inhibition of cell proliferation, acting on ACF in the colonic mucosa.

1,2-Dimethylhydrazine↗

PubMed2001

Detection of p53 gene mutations in human esophageal squamous cell carcinomas using a p53 yeast functional assay: possible difference in esophageal carcinogenesis between the young and the elderly group.

A p53 yeast functional assay, which cannot only detect p53 gene mutations but also can assess p53 gene function, was used to screen for p53 gene dysfunction in human esophageal squamous cell carcinomas. Surgically resected frozen tissues of esophageal squamous cell carcinomas from 57 patients were examined for p53 gene mutation. Because the mean age of the patients diagnosed with esophageal squamous cell carcinoma was 64 years, we classified those who were <65 years of age as the Young Group and classified the others as the Elderly Group. The incidence of p53 gene mutations was 43 of 57 (75%). The incidence of p53 gene mutations observed in the Young Group was significantly higher than in the Elderly Group (P = 0.0007). Alcohol and smoking status did not relate to p53 gene mutation expression. Survival rate after surgery was not significantly associated with the presence of p53 gene mutation. However, in the Young Group with p53 gene mutation, those who had null mutations had a significantly shorter survival than those without null mutations (P = 0.0455). No other clinicopathological factors were associated with p53 gene mutations. Possibly, there may be a difference in esophageal carcinogenesis between the Young and the Elderly groups, because the incidence of p53 gene mutations is different between the two groups. In the Young Group, p53 gene mutation may cause esophageal carcinogenesis, and null mutation for p53 gene is a significant prognostic factor.

Age Factors↗