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Biomedical subjects

N Takada

Publications and source records attributed to N Takada.

At least 109 records · Page 6Linked to original sources

[Effect of FUT-187, oral serine protease inhibitor, on inflammation in the gastric remnant].

Excessive enterogastric reflux following partial gastrectomy is believed to be responsible for the cause of inflammation in the gastric remnant. We examined the effect of FUT-187, a synthetic serine protease inhibitor, on symptoms and endoscopic findings in 33 patients who were diagnosed endoscopically as postgastrectomy gastritis. Patients took 50 mg FUT-187 orally after each meal and at bedtime for 8 weeks. Before treatment, 30 patients (91%) suffered from several symptoms including regurgitation and/or bitter taste in the mouth (49%), epigastric pain (42%) and nausea (36%). From endoscopic observation, erythema was detected in 32 patients, edema in 23 patients and erosion and/or ulcer in 9 patients. After treatment the global improvement rating for subjective symptoms was 76.7% (23/30) and the improvement of endoscopic findings was 63.6% (21/33). Diarrhea was observed in one patient but could be easily controlled by discontinuation of the drug. Our results suggest that FUT-187 can be a useful drug for the treatment of postgastrectomy gastritis with its efficacy and safety.

Administration, Oral↗

Expression of immunoreactive human hepatocyte growth factor in human esophageal squamous cell carcinomas.

Hepatocyte growth factor (HGF) is a potent mitogen for epithelial cells that promotes cell motility and invasiveness. In this study, we report that the human esophageal squamous cell carcinoma (SCC) shows a significant elevation of HGF concentration (600 +/- 416 ng/100 mg protein), compared to normal mucosa (80 +/- 183 ng/100 mg protein) (P < 0.01). An association could be established between levels of HGF and decreasing differentiation of 37 SCCs. The 2-year crude survival rates were 51.1% and 68.4% at high and low HGF concentrations, respectively. The results indicate that HGF is significantly increased in human esophageal SCCs, especially of poorly differentiated type. HGF might thus be useful as a biological biomarker for characterization of human esophageal SCCs.

Adult↗

Prognostic significance of the MIB-1 proliferation index for patients with squamous cell carcinoma of the esophagus.

BACKGROUND: A number of studies have indicated that the ki-67 proliferation index is of important prognostic significance for a variety of neoplasias. It was the aim of this study to investigate whether any correlation exits between the MIB-1 proliferation index and various clinicopathologic parameters in squamous cell carcinomas of the esophagus from 72 patients (20 women: median age, 64 years; range, 45-79 years; and 52 men: median age, 61 years; range, 43-77 years). METHODS: Proliferative activity was determined using an immunohistochemical method with monoclonal antibody MIB-1 (ABC method), for tumor samples obtained from individuals who underwent esophagectomy in the period from 1983 to 1991. The percentage proliferation index (PI) was calculated as the number of positive cells divided by the total number of cells examined. Thirty-nine patients (54%) died of recurrence of esophageal cancer, with a median survival span of 15 months (range, 1-58 months). Thirty-three patients (46%) were still alive at the time of this study; their median follow up was 57 months (range, 40-98 months). RESULTS: Significant differences between proliferative index values were recorded for the following parameters: survival rate, P < 0.0001; presence of lymph node metastasis, P < 0.05; size of the primary esophageal lesion, P < 0.01; proliferation pattern of the tumor, P < 0.01; and age of the patients, P < 0.05. No correlation was found regarding histologic differentiation, clinical stage, location of the lesion, intraepithelial cancerous spread, lymphatic and blood vessel invasion, and sex of the patients. CONCLUSION: The MIB-1 proliferation index may be a powerful prognostic marker for patients with squamous cell carcinomas of the esophagus.

Adult↗

Validation of silver-stained nucleolar organizer regions for evaluation of invasive character of urinary bladder carcinoma in rats and mice.

A series of 8 rat and 16 mouse invasive bladder carcinomas were investigated for the presence of silver-stained nucleolar organizer regions (AgNORs) to clarify whether this parameter is applicable to the estimation of their invasive character. With regard to number of AgNORs per cell, neither rat nor mouse carcinomas showed any difference between invasive and noninvasive sites within the same tumor. However, the frequency of cancer cells bearing bizarre dots, irregular in size and shape, was significantly higher at sites of actual invasion. Quantitative data generated using an image analyzer revealed significantly lower values for NOR roundness and significantly larger NOR size in invasive sites than in noninvasive sites in all groups. Double staining for the proliferation marker proliferating cell nuclear antigen (PCNA) and AgNORs was performed on eight rat carcinomas and a close correlation between the two was confirmed. Thus the number of AgNORs in PCNA-positive cells was significantly greater than in PCNA-negative cells. Furthermore, a particularly strong correlation was observed for incidences of PCNA-positive cells and bizarre dots (P < 0.01). The quantitative data also demonstrated significant differences in size and shape of dots. It is concluded that AgNORs have diagnostic value for the invasive character of bladder carcinomas.

Animals↗

Prevalence of antibodies to Borrelia spirochetes among wild small rodents in central and western Japan.

Field rodents serve as a reservoir for Lyme disease spirochetes. To evaluate the antibody responses of rodents against different Borrelia species in relation to fauna of vector ticks feeding on them, we examined 272 sera of wild rodents, Apodemus speciosus, A. argenteus, and Eothenomys smithii, obtained in 27 locations in central and western Japan from 1981 to 1994. As to prevalences by rodent species using immunoperoxidase test, A. speciosus, A. argenteus and E. smithii showed 29.4%, 11.6% and 30.8% reactivity to Borrelia japonica, 10.7%, 7.2% and 3.8% to B. afzelii, 0.6%, 1.4% and 0% to B. garinii, and 14.7%, 7.2% and 11.5% to an unknown Borrelia species designated as It type, respectively. Each antibody to B. japonica, B. afzelii and B. sp. It type was detected widely both in central and western Japan, but the antibody to B. garinii was scarcely detectable in any area and rodent species examined. Apodemus mice in high mountain altitudes tend to have antibody to B. afzelii or B. japonica, and those in lower altitudes tend to have B. japonica or B. sp. It type. All 13 Apodemus mice from which B. japonica or B. sp. It type were isolated showed higher titers of antibodies to each homologous Borrelia species. The present results indicate that these antibody prevalences among rodents may be associated with dominant Ixodes ovatus and sporadic I. persulcatus on the mainland of Japan, and that Apodemus mice may not be an efficient reservoir for B. garinii. Such a serosurvey is a useful measure to evaluate the natural distribution of the pathogen.

Animals↗

Identification of spirochetes isolated from wild rodents in Japan as Borrelia japonica.

Spirochetes isolated from three species of wild mice, Apodemus speciosus, Apodemus argenteus, and Eothenomys smithi, which were caught on Honshu, Japan, were characterized on the bases of protein profiles, reactivities with monoclonal antibodies (MAbs), and DNA homology values. All the isolates reacted with MAb O1441b, which is specific for Borrelia japonica, but not with MAb P62, which is specific for Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii. The DNA relatedness of four representatives isolates to strain HO14, a type strain of B. japonica, was 83 to 88%. From these findings, the spirochetes were identified as B. japonica.

Animals↗

[Chemosensitivity test for thyroid cancer by in vitro MTT assay].

In vitro MTT assay was applied for examining chemosensitivity with 50 thyroid cancers; 47 papillary cancers, 1 follicular cancer, 1 anaplastic cancers, and 1 medullary cancer. Anticancer drugs examined were 5-fluorouracil (5-FU), cisplatin (CDDP), adriamycin (ADM), etoposide (VP-16) and ifosfamide (IFO) (active type). Their efficacy was as follows: 5-FU 0%, CDDP 40.9%, ADM 0%, VP-16 5.3%, IFO 48.5%. Anaplastic cancer and medullary cancer showed no sensitivity to all tested drugs. We compared the chemosensitivity between cancer tissue and normal tissue. CDDP was more effective in cancer tissue than in normal tissue. Chemosensitivity of CDDP depended on the drug concentration but 5-FU did not. CDDP and IFO might be useful against human differentiated thyroid cancer.

Antineoplastic Agents↗

Dose-dependent inhibition of glutathione S-transferase placental form-positive hepatocellular foci induction in the rat by methyl propyl disulfide and propylene sulfide from garlic and onions.

Two organosulfur compounds, methyl propyl disulfide (MPD) and propylene sulfide (PS) from garlic and onions, were studied for their modifying effects on hepatocarcinogenesis in the F344 rats. Modifying potential was scored by comparing the number and area per cm2 of induced glutathione S-transferase placental form (GST-P)-positive foci in the liver. MPD and PS significantly reduced both these parameters of GST-P-positive foci in a dose-dependent manner. To investigate possible mechanisms of inhibition, ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SAT) activities were measured. In MPD and PS-high dose-treated liver tissue there was a tendency for their decrease, albeit non-significant, which suggested that the inhibitory effect might have been caused by decreased cell proliferation associated with decreased polyamine biosynthesis. In evaluating relationships between diet and cancer, it is thus necessary to consider various effects in assessing possible protective roles of garlic and onions.

Allium↗

22-Oxa-1,25(OH)2vitamin D3, a synthetic analogue of vitamin D3, has no promoting activity in a rat liver medium-term bioassay.

Modifying effects of 22-oxa-1,25(OH)2vitamin D3(OCT), a synthetic analogue of vitamin D3, were evaluated in a liver medium-term bioassay using glutathione S-transferase placental form (GST-P)-positive foci and 5-bromo-2'-deoxyuridine (BrdU) labeling to give an index of DNA synthesis. F344 rats were given a single intraperitoneal injection of diethylnitrosamine (200 mg/kg body wt.) and subjected to two-thirds partial hepatectomy at week 3. Commencing 2 weeks from the start, 500 p.p.m. phenobarbital sodium and/or basal diet were fed to the rats for 6 weeks, at the same time as OCT and/or propylene glycol as the vehicle injected intraperitoneally 5 times a week. OCT demonstrated no promoting activity for rat hepatocarcinogenesis, and, in fact, showed a tendency to decrease the area per unit area of (GST-P)-positive foci in the livers of rats fed 500 p.p.m. phenobarbital sodium. However, intergroup differences in areas and numbers per unit area as well as in BrdU labeling indices were not statistically significant.

Animals↗

Enhancement by organosulfur compounds from garlic and onions of diethylnitrosamine-induced glutathione S-transferase positive foci in the rat liver.

Ten organosulfur compounds from garlic and onions were studied for their modifying effects on diethylnitrosamine-induced neoplasia of liver in male F344 rats using the medium-term bioassay system of Ito based on the two-step model of hepatocarcinogenesis. Carcinogenic potential was scored by comparing the number and area per cm2 of induced glutathione S-transferase placental form-positive foci in the liver with those of the corresponding control group given diethylnitrosamine alone. In experiments 1 and 2, high doses of diallyl sulfide, diallyl trisulfide, allyl methyl sulfide, allyl methyl trisulfide, and dipropyl sulfide had enhancing effects on focus formation. In contrast, high doses of methyl propyl disulfide and propylene sulfide significantly decreased the number of glutathione S-transferase placental form-positive foci. In the third experiment, combined treatment with the five chemicals that had enhancing activity were fed at low doses and increased the induction of glutathione S-transferase placental form-positive foci. To investigate the mechanism of the modifying effect on hepatocarcinogenesis, ornithine decarboxylase activity was measured in diallyl sulfide-, allyl methyl sulfide-, and dipropyl sulfide-treated liver tissue without prior initiation with diethylnitrosamine, and its activity was increased compared to controls. Spermidine/spermine N1-acetyltransferase activity was not significantly changed. Formation of 8-hydroxydeoxyguanosine, a DNA adduct generated by activated oxygen species, and lipid peroxidation (2-thiobarbituric acid-reacting substance production) were also not changed. These results suggest that the promoting effect could be caused by increased cell proliferation with increased polyamine biosynthesis. In evaluating relationships between diet and cancer, it is appropriate to consider not only the possible protective role of garlic and onions but also their enhancing effects.

Allium↗

A defective non-LTR retrotransposon is dispersed throughout the genome of the silkworm, Bombyx mori.

The presence of long repetitive sequences is demonstrated in the genome of the silkworm, Bombyx mori. Members of this BMC1 family reveal several features typical of the L1 (long interspersed sequence one) family of mammals, except for species specific elements. The number of BMC1 elements is estimated to be approximately 3500 per haploid genome. Elements containing the full length unit of 5.1 kb are dispersed throughout the genome and their restriction sites are conserved, although most members are preferentially truncated to varying extents at their 5' ends. DNA sequencing indicates that this element contains six tandem repeats of 15 bp CpG-rich sequence in the 5' proximal region. It terminates with a 3' oligo(A) stretch, and is flanked at both ends by a 7-10 bp target sequence duplication. In addition, there is significant evidence for amino acid sequence homology with reverse transcriptase domains of other L1 families, especially F, Doc and Jockey of Drosophila melanogaster. No large open reading frame is present. The BMC1 element is suggested to be dispersed in the genome by a transposition mechanism involving RNA intermediates.

Amino Acid Sequence↗

p53 mutations in early neoplastic lesions of the urinary bladder in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

Rat experimental models using N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as an initiating agent have been widely used to study carcinogenic processes in the urinary bladder. In this study, early neoplastic lesions from 10 male F344 rats treated with 0.05% BBN for 16 weeks were analyzed for changes in the H-ras or p53 genes by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis and subsequent DNA sequencing. Lesions were pooled for each of the 10 rats and six showed point mutations in the p53 gene and one in the H-ras gene. These results would indicate that BBN-induced rat urinary bladder carcinomas are similar to human urinary bladder carcinomas with respect to alterations in the p53 and H-ras genes and that p53 gene alterations are relatively early events in rat urinary bladder carcinogenesis induced by BBN treatment.

Animals↗

First isolation of a rickettsia closely related to Japanese spotted fever pathogen from a tick in Japan.

In May 1993, we collected unfed ticks in Anan, Tokushima Prefecture, Shikoku District, Japan, a highly endemic area of Japanese spotted fever (JSF). We isolated JSF rickettsiae from these ticks by inoculating tick-emulsions into L-929 cells. Of the four genera and seven species of ticks examined, only one larva of Dermacentor taiwanensis Sugimoto yielded a rickettsial isolate. The isolate (DT-1 strain) was found to belong to the serotype common to the causative agent of JSF. This was based on its specific reactivity to mouse antisera and to a monoclonal antibody to JSF rickettsiae from the Shikoku District. This is the first tick-borne spotted fever group of rickettsia isolated in Japan. However, all stages of D. taiwanensis infrequently parasitize humans. Some ticks in the genus Haemaphysalis commonly infest humans and are frequently found to be rickettsia-positive in the hemolymph test when using the monoclonal antibody mentioned above. Therefore, the vectors of JSF rickettsiae to humans may be a complex of tick species.

Animals↗

Prevalence of Lyme borrelia in ticks, especially Ixodes persulcatus (Acari: Ixodidae), in central and western Japan.

Prevalence of Lyme Borrelia in unfed ticks was surveyed in central and western Japan during spring from 1991 to 1993. The tick fauna was diverse; ticks obtained consisted of four genera and more than 12 identified species, and both southern and northern species coexist with altitudinal separation. Midguts of ticks were cultured in BSK medium for spirochetal isolation. Borrelia-positive rates for adults of both a common species, Ixodes ovatus Neumann, and a northern species, Ixodes persulcatus Schulze, in the extreme western part of the Japanese central mountainous zone (Fukui and Gifu prefectures) were 18.1 and 12.9%, respectively. A Borrelia-positive nymph of Haemaphysalis flava Neumann also was found for the first time in Japan. In contrast, I. persulcatus in southwestern Japan was localized in mountains with elevations over 800 m and was determined negative for Borrelia, whereas I. ovatus was highly positive (28.8%). These Borrelia isolates were diverse in typing of protein profiles. Our results reveal that I. persulcatus-borne Borrelia derived from northern Japan is kept within the limits of the western extremity of the central mountainous zone.

Animals↗

Enhancing effects of organosulfur compounds from garlic and onions on hepatocarcinogenesis in rats: association with increased cell proliferation and elevated ornithine decarboxylase activity.

Four organosulfur compounds from garlic and onions were examined for modifying effects on diethylnitrosamine (DEN)-induced neoplasia of the liver in male F344 rats using the medium-term bioassay system based on the two-step model of hepatocarcinogenesis. Carcinogenic potential was scored by comparing the numbers and areas per cm2 of induced glutathione S-transferase placental form-positive foci. Isothiocyanic acid isobutyl ester (IAIE), dipropyl trisulfide (DPT), and allyl mercapton (AM) exerted enhancing effects on their development, while dimethyl trisulfide also tended to increase them. To investigate possible mechanisms of the modifying influence, sequential changes in ornithine decarboxylase activity (ODC) over 24 h were measured in AM-treated liver tissue without prior DEN initiation. The activity started to increase by 4 h after AM-treatment, and reached maximum at 16 h, compared to controls. Spermidine/spermine N1-acetyltransferase activity was not significantly changed. An increase in proliferating cell nuclear antigen-positive cells followed the elevation of ODC activity. These results suggest that IAIE, DPT, and AM promote rat hepatocarcinogenesis and their promoting effect might be caused by increased cell proliferation with increased polyamine biosynthesis. In evaluating relationships between diet and cancer, it is thus appropriate to consider not only a possible protective role of garlic and onions, but also enhancing effects.

Acetyltransferases↗