Biomedical subjects

M Tamura

Publications and source records attributed to M Tamura.

At least 271 records · Page 15Linked to original sources

PubMed1998

Transduction of glioma cells using a high-titer retroviral vector system and their subsequent migration in brain tumors.

The intracranial migration of transduced glioma cells was investigated in order to improve the treatment of malignant glioma by gene therapy using retroviral vectors. In this study, about half the volume of the tumor mass could be transduced in 14 days after only a single implantation of 3 x 10(5) retrovirus-producing cells into a tumor mass with a diameter of 5 mm. Moreover, we were able to follow the migration of glioma cells transduced by the lacZ-harboring retroviruses originating from the high-titer retrovirus-producing cells. Besides the importance of using a high-titer retroviral vector system, our results also indicate that the implantation site of the virus-producing cells and the interval between the implantation of the virus-producing cells and the subsequent administration of ganciclovir are important factors for the efficient killing of glioma cells.

Animals↗

PubMed1998

Coelomic pouch formation in reconstructing embryos of the starfish Asterina pectinifera.

The morphogenetic processes of coelomic pouch (CP) formation in starfish embryos that were experimentally dissociated and induced to undergo reconstruction were studied. An analysis of these embryos randomly chosen from several cultures showed that CP always form on either side of the esophagus, even though the CP formation can differ in timing of initiation and duration, and can vary in number and size from embryo to embryo. Successive observations of CP formation in living embryos revealed two distinct sequences of CP development that were accompanied by different appearances of the blastocoele. These processes were named 'enterocoelic-like' and 'schizocoelic-like' CP formation. The former resembled normal development and occurred in embryos with a transparent blastocoele. The latter was characterized by the aggregation and epithelialization of mesenchyme-like cells on either side of the esophagus and was observed in embryos possessing a cloudy blastocoele. In a few embryos, both types of CP formation were seen in the same individual ('mosaic type' CP formation). Thick sections of embryos possessing a cloudy blastocoele revealed that aggregates of mesenchyme-like cells undergoing CP formation directly contact the developing esophagus. Together, these data demonstrate flexibility in the morphogenetic processes that regulate CP formation, and suggest that positional cues in the esophagus regulate the placement of CP.

Animals↗

PubMed1998

Immediate effects of extracorporeal shock waves on the male genital system of rabbit. Preliminary report.

Hemospermia was reported to occur following extracorporeal shock wave lithotripsy of lower ureteric stones. Because no studies showed clearly the possible effect of extracorporeal shock waves (ESW) on the male genital system, we were prompted to study this effect. Eighteen male white New Zealand rabbits were divided into three groups (six in each) and subjected to different doses of ESW (2000, 3000 and 4000) using a Dornier MFL 5000. Shocks were focused on the lower parts of the bladder. Four animals were used as controls. Two hours later, the animals were dissected. Gross examination of the genital systems showed bleeding in the testicles and prostates of only some animals, whereas microscopic examination revealed bloody spots in the genital structures of all animals. The amount of bleeding was ESW dose-independent. In conclusion, ESW showed evident immediate effects on the male genital system. Application of shock waves in treating lower ureteric or vesical stones in doses between 2000 and 4000 may cause bleeding in the structures of this system, which can lead to hemospermia. More studies will be needed to show the long-term sequelae of these changes on the male genital system.

Animals↗

PubMed1998

Immunization with the N-terminal region of the nonstructural protein NS1 promotes survival after challenge with lethal influenza A virus dose.

We previously reported that the epitope recognized by an influenza A virus H1, H2, and H3-crossreactive, H-2 Ld-restricted CD8+ cytotoxic T lymphocyte (CTL) is located between amino acids 1 and 40 on the nonstructural protein NS1. In the present experiments, we examined whether immunization with recombinant vaccinia virus which contained genes coding for amino acids 1-40 of NS1 (Vac-10) protected mice from lethal challenge with influenza A virus. Mice immunized with this recombinant virus developed influenza A virus-specific cytotoxic activity but not neutralizing antibodies. Challenge with a lethal dose of influenza A virus demonstrated that the first deaths were delayed by 2 days, and the mortality rate was significantly reduced (p < 0.05) in Vac-10-immunized mice compared with mice immunized with control vaccinia virus. These results suggest that immunization with a single subtype-crossreactive CTL epitope on NS1 can induce protective immunity against lethal influenza A virus infection.

Animals↗

PubMed1998

Relation of serum total cholesterol, serum triglycerides and fasting plasma glucose to colorectal carcinoma in situ.

BACKGROUND: No one has previously examined the relation of serum total cholesterol, serum triglycerides and fasting plasma glucose to colorectal carcinoma in situ. METHODS: A case-control study was performed with 129 cases of colorectal carcinoma in situ and 258 matched controls among examinees undergoing a health check-up in Tokyo from January 1991 to March 1993. RESULTS: There was a significant, positive association between serum total cholesterol levels and the risk of colorectal carcinoma in situ after adjustment for age, sex, body mass index, smoking status and alcohol consumption. Serum triglyceride levels were significantly and positively associated with colorectal carcinoma in situ risk regardless of adjustment for the above covariates. Although there was no clear relation between colorectal carcinoma in situ and fasting plasma glucose levels, a modest increase of colorectal carcinoma in situ risk was observed in the highest category (> or =116 mg/dl) of fasting plasma glucose levels. CONCLUSIONS: The findings suggest a positive association between serum total cholesterol levels and the risk of colorectal cancer, rather than an inverse relation. The strong association with serum triglyceride levels and the weak association with fasting plasma glucose levels support the hypothesis that hyperinsulinaemia may play an important role in colorectal carcinogenesis.

Adult↗

PubMed1998

Expression of interleukin-1beta mRNA and protein in human gliomas assessed by RT-PCR and immunohistochemistry.

To characterize the expression and localization of interleukin (IL)-1beta in human gliomas, both reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were used on surgically excised human gliomas, human malignant glioma xenografts, and human glioblastoma cell lines. The RT-PCR products for IL-1beta mRNA were quantified by computerized image analysis. IL-1beta mRNA was detectable in 30 out of 35 (86%) surgically resected gliomas. An abundant expression of IL-1beta mRNA was often found in the glioblastomas, anaplastic astrocytomas, and pilocytic astrocytomas, but not in other types of gliomas. Quantitatively, in both the grade 2 astrocytomas and the oligodendrogliomas, the IL-1beta mRNA levels were significantly (p < 0.05) lower than those of the grade 3/4 astrocytomas. Immunohistochemically, IL-1beta was localized in the pleomorphic tumor cells of the astrocytic tumors and in macrophages. In contrast to the astrocytic tumors, low and high grade oligodendrogliomas showed no or little expression of IL-1beta antigen. IL-1beta was present less frequently than IL-1alpha and IL-1 receptor type 1 in 4 malignant gliomas transplanted into nude mice by RT-PCR. All 2 cell lines showed IL-1beta expression at both the mRNA and protein levels. It is concluded that in human gliomas, both high-grade astrocytomas and pilocytic astrocytomas often express high IL-1beta production, and that IL-1beta is mainly localized in astrocytic tumor cells and macrophages.

Adolescent↗

PubMed1998

Renal angiotensin converting enzyme promotes renal damage during ureteral obstruction.

PURPOSE: We and others have shown that angiotensin II has a pivotal role in renal damage in various renal injuries. Although most angiotensin II actions are associated with the angiotensin type 1 receptor, there is increasing evidence that the angiotensin type 2 receptor also transduces some important effects of angiotensin II. In this regard we recently observed that mice with genetically engineered disruption of the angiotensin type 2 receptor, termed Agtr2 mutants, are more susceptible to structural renal damage after ureteral obstruction. Recent evidence suggests that a genetically determined increase in angiotensin converting enzyme activity in humans promotes end organ damage. Therefore, we determined whether renal damage in Agtr2 mutants is associated with heightened angiotensin converting enzyme activity. MATERIALS AND METHODS: We studied 28 wild type and 19 Agtr2 mutant mice with unilateral ureteral obstruction. Seven days after obstruction was created serum samples were obtained to evaluate angiotensin converting enzyme activity. The obstructed and contralateral kidneys were harvested for histological analysis and determination of renal angiotensin converting enzyme activity by high pressure liquid chromatography. RESULTS: Renal angiotensin converting enzyme was uniformly higher than serum angiotensin converting enzyme in normal wild type and Agtr2 mutant mice. However, even at baseline Agtr2 mutant mice had strikingly higher renal angiotensin converting enzyme activity than normal wild type mice (mean plus or minus standard error 1,492+/-83 versus 450+/-60 milliunits per gm. tissue weight, p <0.0005). Histological analysis revealed more extensive parenchymal damage in the obstructed kidneys of mutant mice than in identically treated controls. Notably while unilateral ureteral obstruction decreased renal angiotensin converting enzyme activity in each group, activity remained persistently higher in the Agtr2 mutants than in normal mice (mean 742+/-146 versus 310+/-43 milliunits per gm. tissue weight, p <0.005). CONCLUSIONS: We propose that elevated renal angiotensin converting enzyme activity contributes to more severe renal parenchymal damage in ureteral obstruction by promoting the availability of growth factors, such as angiotensin II, or depleting antiproliferation factors, such as bradykinin or nitric oxide. These findings complement previous observations that angiotensin converting enzyme inhibition preserves the renal parenchyma after injury, including obstruction.

Animals↗

PubMed1998

Cytopathic effects of the major surface protein and the chymotrypsinlike protease of Treponema denticola.

Prominent antigens of Treponema denticola have been suggested to be mediators of the cytopathic effects typically seen in periodontal disease. In the present study of the T. denticola major surface protein (Msp) and the surface-expressed chymotrypsinlike protease complex (CTLP), we characterized the ability of these proteins to adhere to and lyse epithelial cells. Msp and CTLP were closely associated in spirochete outer membranes. Purified Msp, both native and recombinant, and CTLP bound to glutaraldehyde-fixed periodontal ligament epithelial cells. Adherence of Msp was partially blocked by specific antibodies. Adherence of CTLP was partially blocked by serine protease inhibitors and was further inhibited by specific antibodies. Both native Msp and CTLP were cytotoxic toward periodontal ligament epithelial cells, and their cytotoxicity was inhibited by the same treatments that inhibited adherence. Msp, but not CTLP, lysed erythrocytes. Msp complex (partially purified outer membranes free of protease activity) was cytotoxic toward a variety of different cell types. Pore-forming activities of recombinant Msp in black lipid model membrane assays and in HeLa cell membranes were similar to those reported for the native protein, supporting the hypothesis that Msp cytotoxicity was due to its pore-forming activity.

Animals↗

PubMed1998

Definition of amino acid residues on the epitope responsible for recognition by influenza A virus H1-specific, H2-specific, and H1- and H2-cross-reactive murine cytotoxic T-lymphocyte clones.

We defined the epitopes recognized by three influenza A virus-specific, H-2Kd-restricted CD8(+) cytotoxic T-lymphocyte (CTL) clones: H1-specific clone A-12, H2-specific clone F-4, and H1- and H2-cross-reactive clone B7-B7. The A-12 and B7-B7 clones recognized the same peptide, which comprises amino acids 533 to 541 (IYSTVASSL) of A/PR/8 hemagglutinin (HA). The F-4 and B7-B7 clones both recognized the peptide which comprise amino acids 529 to 537 (IYATVAGSL) of A/Jap HA. Amino acids 533 to 541 of A/PR/8 HA are compatible with amino acids 529 to 537 of A/Jap HA. Amino acid S at positions 3 and 7 was responsible for recognition by H1-specific clone A-12, while amino acid G at position 7 was responsible for recognition by H2-specific clone F-4. Two conserved amino acids, T at position 4 and A at position 6, were responsible for recognition by H1-, and H2-cross-reactive clone B7-B7. These results indicate that a single nine-amino-acid region is recognized by HA-specific CTL clones of three different subtype specificities and that the amino acids responsible for the recognition by the CTL clones are different.

Amino Acid Sequence↗

PubMed1998

Energy-dependent redox state of heme a + a3 and copper of cytochrome oxidase in perfused rat brain in situ.

Using the blood-free perfused rat brain, we examined the redox behavior of cytochrome oxidase of two chromophores, heme a + a3 and copper. When perfusate inflow was stopped to induce global ischemia, the reduction of heme a + a3 was triphasic, with a rapid phase, a slow phase, and a second rapid phase. In contrast, the reduction of copper was monophasic after the rapid phase of heme a + a3. The triphasic reduction of heme a + a3 was diminished by energy-depleting treatments, such as addition of an uncoupler. The time course of the reduction of copper was not affected by the energy depletion. During global ischemia the decrease in creatine phosphate nearly paralleled the reduction of heme a + a3, whereas ATP remained at the control level until approximately 60% of heme a + a3 was reduced in the rapid phase. In the slow phase, ATP started to decrease with the reduction of copper. The redox behavior of copper was similar to the slow phase of the reduction of heme a + a3 because of the higher oxygen affinity of copper than of heme a + a3. Therefore, the rapid phase of the reduction of heme a + a3 can be used as an alarm before a decrease in ATP, whereas the reduction of copper indicates a decrease in ATP under severe hypoxia. Thus the copper signal in noninvasive near-infrared spectroscopy is a useful parameter for the clinical setting.

Animals↗

PubMed1998

Dual regulatory effects of interferon-alpha, -beta, and -gamma on interleukin-8 gene expression by human gingival fibroblasts in culture upon stimulation with lipopolysaccharide from Prevotella intermedia, interleukin-1alpha, or tumor necrosis factor-alpha.

In a previous study, we demonstrated that the amount of interleukin (IL)-8 mRNA expressed by human gingival fibroblasts stimulated with lipopolysaccharide (LPS) from Prevotella intermedia ATCC 25611 is increased by pre-treatment with beta or gamma interferon (IFN-beta or -gamma). In the present study, we identified the regulatory effects of these IFNs on IL-8 mRNA expression and IL-8 production by human gingival fibroblasts. Priming with IFN-alpha (alpha), -beta, or -gamma upregulated the IL-8 mRNA expression in response to P. intermedia LPS, whereas co-stimulation with these IFNs reduced the amount of mRNA expressed by the cells. The regulation of IL-8 mRNA expression induced by recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) or rHuIL-1alpha was similar to that induced by LPS. The IL-8 mRNA expression in response to P. intermedia LPS was enhanced by IFN-gamma independently of de novo protein synthesis, and was regulated, at least in part, at the transcriptional level. The IL-8 mRNA accumulation in response to P. intermedia LPS was inhibited by tosylphenyl-alanyl chloromethyl-ketone, an inhibitor of NF-kappaB activation, although the NF-kappaB activation itself was not altered by IFN-gamma. These findings suggest that IFNs might be capable of both enhancing and inhibiting inflammatory responses in periodontal tissues through the dual regulation of IL-8 production by gingival fibroblasts in response to bacterial components and cytokines.

Blotting, Northern↗

PubMed1998

Role of apoptosis of thyrocytes in a rat model of goiter. A possible involvement of Fas system.

Apoptosis, a physiological process of cell death, may modulate the mass of the thyroid gland. We investigated the role of apoptosis and the possible involvement of Fas/Fas ligand (FasL) system in apoptosis during goiter formation and involution in a rat model of goiter. Rats were fed a low iodine diet and a goitrogen, 6-propyl-2-thiouracil, to induce goiter. Rats with goiter were then fed a high iodine diet to study the phase of involution. We examined the presence of apoptosis by electron microscopy (EM) and terminal deoxy-UTP nick end labeling (TUNEL). We also investigated the association between Fas and FasL expression and thyrocyte apoptosis using immunohistochemistry and Western blotting. To evaluate the proliferation of thyrocytes, proliferating cell nuclear antigen was examined immunohistochemically. The number of apoptotic cells increased during goiter formation and the early stage of involution, which were also associated with increased number of Fas-positive thyrocytes, and some of these cells contained TUNEL-positive nuclei. However, the expression of FasL was almost constant throughout the experiment. Proliferating cell nuclear antigen/TUNEL ratio markedly increased during goiter formation but decreased particularly during the late stage of goiter involution. Our results indicate that apoptosis of thyrocytes is a main factor of cell loss during goiter formation and involution and suggest that the Fas/FasL system is involved in the induction of apoptosis of these cells. Moreover, the delicate balance between apoptosis and cell proliferation may play an important role in the control of thyroid gland mass.

Animals↗

PubMed1998

Recombinant human basic fibroblast growth factor accelerates fracture healing by enhancing callus remodeling in experimental dog tibial fracture.

Effect of recombinant human basic fibroblast growth factor (bFGF) on fracture healing was investigated using a tibial fracture in beagle dogs. Transverse fractures in the middle of the diaphyses were created in the right tibiae and bFGF was injected into the fracture sites at a single dose of 200 micrograms. The time course of changes in callus volume and morphology of the fracture sites were evaluated at weeks 2, 4, 8, 16, and 32 after treatment, and the fracture strength was analyzed at weeks 16 and 32. At week 2, a radiogram of the fracture site showed obvious membranous ossification in the group injected with bFGF. Basic FGF extended the callus area at week 4 and increased the bone mineral content (BMC) in the callus at week 8. bFGF also increased the osteoclast number in the periosteal callus at weeks 2 and 4. In the bFGF group, a maximal increase in the osteoclast index was found at week 4, and an identical increase was recognized in the control group at weeks 8 and 16. These findings strongly suggested that bFGF stimulated not only callus formation but osteoclastic callus resorption. BMC in the bFGF group was followed by a rapid decrease from week 8, while that in the control group was identical from week 4. Fracture strength of the bFGF group showed significant recovery by week 16, and recovery was still evident by week 32. We conclude that bFGF promotes the fracture healing in dogs by the stimulation of bone remodeling.

Absorptiometry, Photon↗

PubMed1998

Preoperative treatment of growth hormone-producing pituitary adenoma with continuous subcutaneous infusion of octreotide.

Preoperative therapy with octreotide, a long-acting somatostatin analog, suppresses GH hypersecretion, shrinks GH-producing tumors and leads to an improvement in subsequent surgical remission in acromegalic patients. A continuous infusion of octreotide has demonstrated more persistent suppression of GH secretion than intermittent injections, and only a few studies were reported on the effect of the tumor shrinkage with a continuous infusion of a small dose of octreotide. We therefore investigated the preoperative effects of small doses of octreotide (120-240 micrograms/day) administered continuously (with a subcutaneous infusion pump) over a short period (2 or 4 weeks) in nine untreated acromegalic patients. Octreotide therapy resulted in suppression of serum GH and IGF-1 concentrations in 8 out of 9 patients and reduction in pituitary tumor size measured by MRI in all patients (by 7.9 to 38.5%). In particular, considerable reduction in tumor size (more than 20%) occurred in 6 of 9 patients. In three patients assessed serially throughout the preoperative period, reduction in tumor size was noted within only one week after the start of octreotide therapy and reduction rate more than 20% was obtained within the first two weeks. In one patient, suprasellar tumor expansion totally disappeared after such therapy. Our results indicate that short-term continuous subcutaneous infusion of a small dose of octreotide results in not only inhibition of GH hypersecretion but also shrinkage of tumor size prior to surgery.

Adenoma↗

PubMed1998

Relationship between MLR blocking antibodies and the outcome of the third pregnancy in patients with two consecutive spontaneous abortions.

To determine the relationship between mixed lymphocyte culture reaction (MLR) blocking antibodies (BAbs), immunological humoral factors, which generated in pregnant women and the outcome of pregnancy, the natural outcome of the third pregnancy in fifty-five patients with primary twice consecutive abortion was evaluated, and MLR-BAbs in sera were examined during their third pregnancy. The third pregnancy in 39 of 55 patients (70.9%) continued successfully, and remaining 16 patients (29.1%) experienced repeated abortion at the first trimester. Out of these 55 patients, MLR-BAbs were examined in 27 (17 with successful outcome and 10 with repeated abortion). The positive rate of MLR-BAbs was 82.4% in patients with successful outcome (15 of 17 cases), and that in patients with repeated abortion was 10% (one of 10 cases). The positive rate of MLR-BAbs was significantly higher in the successful pregnancy group compared with that in the repeated abortion group (p < 0.001). The blocking effect on MLR significantly increased along with the prenatal course in patients with successful outcome. Thus, MLR-BAbs are strongly associated with the outcome of pregnancy in patients with primary twice consecutive spontaneous abortions.

Abortion, Habitual↗

PubMed1998

Anti-cardiolipin antibody and anti-cardiolipin beta-2-glycoprotein I antibody in patients with recurrent fetal miscarriage.

To elucidate the association between anticardiolipin antibody (aCL-Ab) or anti-cardiolipin beta-2-glycoprotein I-antibody (aCL-beta-2-GP I-Ab) and recurrent fetal miscarriage, the positive rates of aCL-Ab were assessed in 667 patients with recurrent fetal miscarriages and those of aCL-beta-2-GP I-Ab were assessed in 208 patients. The rates were then compared with the control group. The positive rate of aCL-Ab in the patients group (17.4%) was significantly higher than that in the control group (4.0%). The rate of aCL-Ab was especially high in patients who had experienced two or more fetal miscarriages including at least one or more intrauterine fetal deaths during the second or third trimester (41.3%). The positive rate of aCL-beta-2-GP I-Ab in patients with recurrent fetal miscarriage (3/208 cases, 1.4%) was not significantly different from the control group (0/100 cases, 0%). However, the rate of aCL-beta-2-GP I-Ab was significantly higher in patients who had experienced two or more fetal miscarriages including at least one or more intrauterine fetal deaths during the second or third trimester (8.3%) compared with the control group. In conclusion, the implication of aCL-Ab in the genesis of recurrent fetal miscarriage was confirmed. It was suggested that aCL-beta-2-GP I-Ab was associated with the generation of intrauterine fetal death, although it had little association with the genesis of recurrent fetal miscarriage during the first trimester.

Abortion, Habitual↗

PubMed1998

Improved survival of children with advanced tumors by myeloablative chemotherapy and autologous peripheral blood stem cell transplantation in complete remission.

Five children with neuroblastoma (NB) stage IV and five children with rhabdomyosarcoma (RMS) stage III were treated with myeloablative chemotherapy and autologous peripheral blood stem cell transplantation (MCT/PBSCT) in the state of complete remission (CR) achieved by conventional therapy. PBSCs were collected in CR status using a cell separator with blood access through a double-lumen central venous catheter. PBSCs with 1.9+/-0.8x10(5) of CFU-GM per patient weights (kg) were infused following MCT after a period of conventional therapy for 11.1+/-2.1 or 9.7+/-0.9 months in NB or RMS patients, respectively. Regimen-related toxicity of MCT was tolerable and peripheral white blood cell count recovered beyond 1.0x10(3)/microl 10-12 days after infusion of PBSCs in all patients. All of RMS patients and three of five NB patients survived for an average of 31.6 months (ranged 10.8-58.1). The survival rate of these patients was improved as compared with our historical controls, and presumably, with that of conventional chemotherapy previously reported. Despite a limited number of patients, it appears that MCT/PBSCT may be effective in improving survival by preventing relapse which may occur thereafter if treated with conventional therapy alone. Furthermore, MCT/PBSCT reduced the duration of treatment, as compared with that of conventional chemo-therapy. Therefore, this study may suggest the feasibility and promise of the therapy including MCT/PBSCT for children with advanced stages of NB and RMS.

Antineoplastic Agents↗

PubMed1998

Prognostic factors of small-cell lung cancer in Okayama Lung Cancer Study Group Trials.

In order to elucidate factors influencing the prognosis of small-cell lung cancer (SCLC), we reviewed the records of 253 patients with SCLC and evaluated 20 pretreatment prognostic factors by univariate analysis and Cox's multiple regression analysis. Recursive partitioning and amalgamation (RPA) was employed to identify subgroups with similar survival rates. Cox's multiple regression analysis identified five significant factors: extent of disease, number of metastatic sites, serum albumin, serum lactate dehydrogenase, and presence of weight loss. Among these, extent of disease was the most influential factor. RPA analysis revealed three subgroups predicting significantly different prognoses. The median survival time and 3-year survival rate were 18.4 months and 20.6%, respectively for the good-risk group (limited disease without weight loss), 13.5 months and 9.1%, respectively for the intermediate-risk group (limited disease with weight loss or extensive disease with less than two metastatic sites), and 9.2 months and 0%, respectively for the poor-risk group (extensive disease with two or more metastatic sites). These results will be useful for development of new staging system or subsequent stratification for randomized trials.

Aged↗