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Biomedical subjects

T Sawada

Publications and source records attributed to T Sawada.

At least 109 records · Page 6Linked to original sources
PubMed2001

Thyroid hormone response element-like sequence in anuran matrix metalloproteinase 1 gene is responsive to in vivo thyroid hormone administration.

Gene (Rmmp1) of matrix metalloproteinase 1 (MMP1) of the bullfrog, Rana catesbeiana, has been shown previously to contain a thyroid hormone response element (TRE)-like sequence in its 5'-upstream region. The present study aimed to determine whether this TRE-like sequence is functional in vivo as a true TRE, and to characterize the sequences of the 5'-upstream region with respect to the regulation of the activity of the TRE when the TRE-like sequence was proved to be a true TRE. With this aim, various sequences of TRE-like sequence-containing 5'-upstream region were constructed and fused to the enhanced green fluorescent protein gene as a reporter gene. The fusion constructs were bombarded to the skin of bullfrog tadpoles and the activity of the TRE was quantitatively determined by measuring increased intensities of fluorescence when the animals were exposed to thyroid hormone. The present study clearly demonstrated that the sequence of Rmmp1 is a biologically active TRE in vivo. In addition, a unique 36 bp long sequence directly flanked to the 3'-end of the TRE was identified which worked co-operatively with TRE to regulate the transcriptional promoter activity. It should be emphasized that the presence of TRE in the Rmmp1 gene is unique, because its presence has not been reported in the known promoter region of vertebrate MMPs.

Animals↗
PubMed2001

Highly sensitive and direct detection of DNA fragments using a laser-induced capillary vibration effect.

A pulsed laser-induced stationary wave capillary vibration detection method was applied to the sensitive detection of capillary gel electrophoresis, and the direct detection of non-labeled nucleic acids, such as DNA sequencing products, was demonstrated. An excimer laser operating at 248 nm was used as a CVL excitation source, and polynucleotides were sensitively detected without derivatization. From an investigation on the endurance of several matrixes to pulsed laser irradiation, a polyacrylamide without a cross-linker (0%C) was found to have adequate endurance, and it exhibited no serious damage during an analysis. A cytosine-terminated sequence reaction product was detected with a sensitivity close to that of laser-induced fluorometry (LIF). These results suggest the feasibility of the highly sensitive detection of ultramicro amounts of biological materials without a pre- or post-column derivatization, which has usually been required in sensitive detection procedures, such as LIF. Furthermore, the feasibility of a novel DNA sequencing method is also suggested.

Acrylic Resins↗
PubMed2001

TGF-beta1 promotes liver metastasis of pancreatic cancer by modulating the capacity of cellular invasion.

We investigated the effect of TGF-beta1 on liver metastasis of pancreatic cancer using surgical specimens of pancreatic cancer and human pancreatic cancer cell lines Capan-2 and SW1990. Immunostaining of TGF-beta1 showed that TGF-beta1 positivity was significantly related to venous invasion and tumor staging, and also relatively associated with liver metastasis. Cellular invasion and protease production of MMP-2 and u-PA, and in vivo liver metastasis were significantly enhanced after treatment of cells with TGF-beta1. These findings suggest that TGF-beta1 might play an important role in enhancing liver metastasis of pancreatic cancer.

Adenocarcinoma↗
PubMed2001

Laying season and egg shell cracks on the growth of Salmonella enteritidis in the egg albumen during storage.

We studied the effects of laying seasons and egg shell cracks on the ability of egg albumen to support the growth of Salmonella Enteritidis (SE) in eggs. Hens eggs used were those laid in February, June, and October in a farm in Japan and stored at 10, 20, and 30 degrees C, and at 30 degrees C after storage at 10 degrees C, immediately after receipt or after cracking the shell. At several-day intervals during storage, the egg contents were poured into a dish, SE was inoculated into albumen, and then the growth of SE during 3 days incubation at 18 degrees C was measured. The results demonstrated that storage temperature and laying season affected the growth of SE in the egg albumen. The proportion of eggs upon which albumen allowed the growth of SE was higher in the eggs stored at 30 degrees C than those stored at 10 degrees C. The growth of SE in eggs was lowest in the following order of laying: February, October, and June. SE grew preferably in albumen of cracked eggs than intact eggs.

Animals↗
PubMed2001

[A case of heparin-induced thrombocytopenia after transurethral resection of prostate during anticoagulant therapy].

A 66-year-old man had been receiving anticoagulant therapy for myocardial infarction with warfarin potassium (abbreviated as warfarin) 2 mg/day. Though he had been treated with tamsulosin hydrochloride 0.2 mg/day as diagnosis of benign prostatic hyperplasia, he experienced severe dysuria and wanted to undergo transurethral resection of the prostate. We decided to continue anticoagulant therapy because cardiologist judged that intermission of anticoagulant therapy could cause myocardial infarction. Warfarin 2 mg/day p.o. was replaced with heparin sodium (abbreviated as heparin) 5000 u x 2/day s.c. 6 days prior to surgery, and anticoagulant therapy was stopped on the day of surgery, but resumed on the following day. Purpura appeared around the extremities 18 days after the surgery. Although coagulation testing was normal, platelet counts had markedly been reduced (2,000/mm3). Platelet counts recovered to a level of 228,000/mm3 13 days after cessation of heparin. No other adverse effects were observed. Heparin-induced thrombocytopenia (abbreviated as HIT) was diagnosed clinically. We consider monitoring of platelets to be necessary because an increasing number of patients are on anticoagulant therapy in Japan, and accordingly, the use of heparin is likely to be increased.

Aged↗
PubMed2001

[Post-genome challenges against inflammatory bowel diseases].

Advancement of genome analysis might give great impact to the treatment of inflammatory bowel diseases(IBD). IBD patients are treated by sulfadrugs, steroids and anti-immune drugs. For difficult cases, leukocytapheresis, beclomethasone dipropionate, anti-TNF therapy, anti-LTB4 therapy and other new methods are applied. Developing epoch-making drugs will be achieved by finding new molecular targets. Histologic identification of dysplasia is important in the surveillance of long-standing ulcerative colitis. The molecular diagnosis is required for the distinction of dysplasia from the regenerative inflammatory changes. P53 immunostaining have been proved useful. Various molecular targets will be taken into discussion as additional procedures. Recent genome analysis have revealed some genetic factors contribute to pathogenesis of IBD, which are HLA, IL4, MUC3, IBD1 locus, IBD2 locus and so on. More information about genes concerning IBD will be provided by analyzing dense SNP map using DNA tip. They will open the way to the tailored therapy.

Biomarkers↗
PubMed2001

[A case of fatal herpes encephalitis presenting massive cerebral hematoma].

A 53-year-old woman was admitted to the hospital because of headache and disturbance of consciousness. She was afebrile. No inflammatory reaction was identified on serologic examination. Radiological findings showed acute-subacute, massive intracerebral hemorrhage in the right temporal lobe, compressing the brain stem contra-laterally. On the day of admission, she underwent a right temporal craniotomy for the removal of the mass lesion. The resected brain tissue demonstrated a small hemorrhage and edema accompanied by the infiltration of lymphoid cells into the subarachnoid space. Several days after surgery, the patient became lethargic and showed urinary incontinence. Late onset of fever and CSF findings suggested she was suffering from viral encephalitis. Serological findings, however, disclosed no antibody production against HSV, HZV, or CMV. For the diagnosis, a biopsy of the brain was carried out and herpes encephalitis was subsequently proved. Unfortunately, her condition deteriorated quickly and she died without anti-viral treatment.

Aged↗
PubMed2001

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (7)--Three-month repeated oral dose toxicity study in juvenile dogs].

To evaluate the repeated oral dose toxicity of Cefmatilen hydrochloride hydrate (S-1090) in juvenile dogs, S-1090 was administered to juvenile beagle dogs at dose levels of 50, 100, 200 and 400 mg potency/kg/day for 3 months. No deaths occurred. Urinalysis in the 400 mg potency/kg group revealed positive reactions of occult blood and protein, and erythrocytes in sediments. Cystitis was observed in the 200 and 400 mg potency/kg groups. In the thyroids, an increased weight in some animals in the groups dosed at 100 mg potency/kg or more and an increased follicular colloid in the 400 mg potency/kg group were observed. However, no related changes were noted in other examination items. Red to dark-red feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet) were observed in all treated groups. Plasma S-1090 concentrations increased in a manner less than dose-proportional. The lesions of urinary bladder were judged as S-1090-induced toxic changes and the NOAEL of S-1090 in this study was assessed to be 100 mg potency/kg/day.

Administration, Oral↗
PubMed2001

[Pancreatic and biliary tract cancers].

There are several tumor markers for pancreatic and biliary tract cancers, such as carcinoembryonal antigen, pancreatic enzyme, carbohydrate antigen and tumor associated gene. CA19-9 and SPan-1, which are type I carbohydrate antigens, are especially useful among these tumor markers. Combination assays of these tumor markers improve the positive rate for these cancers. These tumor markers are useful not only in diagnosis but also in assessing the therapeutic efficacy and early detection of recurrence after operation.

Biliary Tract Neoplasms↗
PubMed2001

Acute myocardial infarction due to a regressed giant coronary aneurysm as possible sequela of Kawasaki disease.

We report on a young patient admitted with an acute myocardial infarction due to a regressed coronary aneurysm who was treated with balloon angioplasty. The wall morphology of the coronary aneurysm using intravascular ultrasound imaging closely resembled that occurring after Kawasaki disease (KD), although our patient had no obvious past history of KD, suggesting so-called atypical KD.

Adult↗
PubMed2001

Effect of a matrix metalloproteinase inhibitor on a lymph node metastatic model of gastric cancer cells passaged by orthotopic implantation.

Lymph node metastasis is the most frequent type of tumor recurrence and is known to be one reason for the poor prognosis in patients with digestive cancer. However, the mechanisms of lymph node metastasis are not clearly understood and a metastatic model will be useful for elucidating factors associated with lymph node metastases. In this study, we investigated the effect of R-94138, a matrix metalloproteinase (MMP) inhibitor, on the lymphnodal metastatic ability of gastric cancer cells using an in vivo orthotopic implantation model in nude mice. Injection of a gastric cancer cell line, MKN-45, into the gastric wall resulted in lymph node metastasis 8 weeks after inoculation. The number of lymph node metastases and the amount of body weight loss significantly decreased by intraperitoneal administration of R-94138. Histologically, lymphatic invasion of cancer cells was found in primary gastric tumors of control mice with lymph node metastasis. However, no lymphatic invasion was observed in the gastric wall of R-94138-treated mice without lymph node metastasis. These findings suggested that the MMP inhibitor, R-94138, could be used in adjunctive therapy for lymph node metastasis in gastric carcinoma.

Acetamides↗
PubMed2001

Induction of fibroblast-like cells from CD34(+) progenitor cells of the bone marrow in rheumatoid arthritis.

To assess the role of bone marrow in the pathogenesis of rheumatoid arthritis (RA), we examined the capacity of CD34(+) cells from bone marrow to generate fibroblast-like type B synoviocytes. CD34(+) cells from the bone marrow of 22 RA patients differentiated into cells with fibroblast-like morphology, which expressed prolyl 4-hydroxylase, in the presence of stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-alpha), much more effectively than CD34(+) cells from bone marrow of 15 control subjects (10 patients with osteoarthritis and 5 healthy individuals). The generation of fibroblast-like cells was not at all observed in cultures with SCF, GM-CSF, and interleukin 4 (IL-4) with or without TNF-alpha. Generation of fibroblast-like cells was correlated with matrix metalloproteinase (MMP)-1 levels in culture supernatants. Thus, MMP-1 levels were significantly higher in TNF-alpha-stimulated cultures of bone marrow CD34(+) cells from patients with RA than in those from the control group. These results indicate that bone marrow CD34(+) cells from patients with RA have abnormal capacities to respond to TNF-alpha and to differentiate into fibroblast-like cells producing MMP-1, suggesting that bone marrow CD34(+) progenitor cells might generate type B synoviocytes and thus could play an important role in the pathogenesis of RA.

Adult↗
PubMed2000

Molecular cloning and characterization of GalNAc 4-sulfotransferase expressed in human pituitary gland.

We have previously cloned chondroitin-4-sulfotransferase (C4ST) cDNA from mouse brain. In this paper, we report cloning and characterization of GalNAc 4-sulfotransferase (GalNAc4ST), which transfers sulfate to position 4 of the nonreducing terminal GalNAc residue. The obtained cDNA contains a single open reading frame that predicts a type II transmembrane protein composed of 424 amino acid residues. Identity of the amino acid sequence between GalNAc4ST and human C4ST was 30%. When the cDNA was transfected in COS-7 cells, sulfotransferase activity toward carbonic anhydrase VI was overexpressed but no sulfotransferase activity toward chondroitin or desulfated dermatan sulfate was increased over the control. Sulfation of carbonic anhydrase VI by the recombinant GalNAc4ST occurred at position 4 of the GalNAc residue of N-linked oligosaccharides. The recombinant GalNAc4ST transferred sulfate to position 4 of GalNAc residue of p-nitrophenyl GalNAc, indicating that this sulfotransferase transfers sulfate to position 4 at the nonreducing terminal GalNAc residue. Dot blot analysis showed that the message of GalNAc4ST was expressed strongly in the human pituitary, suggesting that the cloned GalNAc4ST may be involved in the synthesis of the nonreducing terminal GalNAc 4-sulfate residues found in the N-linked oligosaccharides of pituitary glycoprotein hormones.

Amino Acid Sequence↗
PubMed2000

Eradication of breast cancer xenografts by hyperthermic suicide gene therapy under the control of the heat shock protein promoter.

To investigate the usefulness of heat shock protein (HSP) promoter for breast cancer gene therapy, hyperthermia and HSV thymidine kinase (tk) suicide gene combination therapy was examined with mouse mammary cancer cell line FM3A. HSP promoter activity was markedly increased after heat shock (41-45 degrees C), with maximum activation (about 400-fold) at 3 hr. An in vitro cytotoxic assay showed that HSP-tk-transduced FM3A cells became more sensitive (more than 50,000 times) to ganciclovir (GCV) with heat shock, but untreated cells showed no increased cytotoxic sensitivity to GCV compared with control FM3A cells. In addition to promoter-oriented selective cell killing, a "chemosensitization effect" as a bystander effect was demonstrated by hyperthermia and suicide gene combination therapy, using a non-heat-inducible promoter. Immunohistochemical analysis revealed that this synergistic killing effect was dependent on apoptotic cell death with upregulation of both Fas and FasL (Fas ligand) expression. We also examined the efficacy of HSP-tk gene therapy in vivo by implanting breast cancer in subcutaneous and intraperitoneal models of BALB/c nude mice targeted by the HVJ-anionic liposome method. Significant tumor regression was observed in HSP-tk-transduced tumors followed by hyperthermia therapy, but no such inhibition was noted in either the mock vector transfection or hyperthermia group compared with control tumor-bearing mice. Our results demonstrate that this combination system is synergistically effective in mediating Fas-dependent apoptosis for a specific gene therapy targeting HSP-expressing mammary carcinomas, even in advanced and heat-resistant breast cancer.

Animals↗
PubMed2000

Interaction of excess electrons with water molecules at the early stage of laser-induced plasma generation in water

Forward and backward stimulated Raman scattering (SRS) of OH stretching vibrations are measured when an intense 40 ps pulsed beam is focused into water. Characteristic features related to the interaction of OH groups with excess electrons generated by the strong laser irradiation are observed. The SRS spectra are indicative of the important role which excess electrons play in transient enhancement of the SRS at the initial stage of laser-induced plasma generation in water. The hydration structures around the excess electrons in water are also discussed.

Journal Article↗
PubMed2000

Roles of pulsatile release of LH in the development and maintenance of corpus luteum function in the goat.

The roles of the pulsatile release of LH in the functional development and maintenance of the corpus luteum (CL) during the estrus cycle in the goat were examined using a potent GnRH antagonist. In Experiment 1, to assess the inhibitory effects of the GnRH antagonist on the release of LH during the estrus cycle, 9 goats were divided into 3 groups. Goats in Group I received only saline on Days 0 (day of ovulation), 5, 10 and 15. Goats in Group II received the GnRH antagonist (50 microg/kg, s.c.) on the days mentioned for Group I to inhibit endogenous LH during the periods of luteal development and maintenance. Goats in Group III received saline on Days 0 and 5 and then the GnRH antagonist on Days 10 and 15 to inhibit LH during the period of luteal maintenance. Serial blood sampling took place on Days 1, 3, 5, 8, 13 and 18 to characterize the LH pulses. The LH pulses were observed throughout the estrus cycle in Group I but were completely abolished in Group II. In Group III, the pulsatile release of LH was observed from Day 1 to 8, but the LH pulses were completely abolished on Days 13 and 18. In Experiment 2, 16 goats were divided into the same 3 groups as in Experiment 1 to examine the effects of the GnRH antagonist on the luteal function. The concentration of progesterone in the plasma in Group I increased after ovulation, reached a maximum level around Day 12, and subsequently returned to the basal level on Day 17. The concentrations of progesterone in Group II rose after ovulation, but reached a plateau around Day 6 and maintained the level up to Day 9, then rapidly decreased from Day 9 to 10 to the basal level. The concentrations of progesterone in Group II were lower on Days 7 to 15 than those in Group I (P<0.01). The concentrations of progesterone in Group III increased after ovulation, reached a maximum level around Day 8, then dropped from Day 10 to 13 to the basal level. The concentrations of progesterone in Group III on Days 11 to 15 were lower than those in Group I (P<0.05 on Day 11, P<0.01 on Days 12 to 15). These results demonstrate that endogenous LH is essential for normal development and maintenance of the CL function during the estrus cycle in the goat. Further, this study suggests that while the functional maintenance of the caprine CL depends entirely on LH support, such functional dependence during early CL development is only partial.

Animals↗
PubMed2000

Caspase-3 activation and inflammatory responses in rat hippocampus inoculated with a recombinant adenovirus expressing the Alzheimer amyloid precursor protein.

To elucidate the mechanism of neuronal death in Alzheimer's disease, we investigated the effects of overexpression of wild-type Alzheimer amyloid precursor protein (APP) on neuronal cells and glial cells in vivo. When an APP695-expressing adenovirus was injected into the dorsal hippocampal region, a number of neurons in remote areas were positively stained with anti-APP monoclonal antibody, and underwent severe degeneration from 3 to 7 days after viral inoculation. Most degenerating neurons were immunopositive with both APP and activated caspase-3, but some neurons that expressed activated caspase-3 were not expressing APP from 7 to 14 days after virus injection. In the neighborhood of the degenerating neurons, activated microglia/macrophages, which were identified by the phenotypic marker C3bi receptor (CD11b/c; OX-42), were observed, and some of them appeared to phagocytose the caspase-3-immunopositive degenerating neurons. In addition to microglia/macrophages, infiltrating leukocytes expressing CD45 or CD4 were also detected. These results suggest that the increased accumulation of APP induced not only caspase-3-mediated death machinery, but also inflammatory responses including microglial activation. These inflammatory responses might cause further neurodegeneration through the alternative pathway that might activate the caspase-3-mediated death machinery without APP expression.

Adenoviridae↗