Biomedical subjects

T Moriyama

Publications and source records attributed to T Moriyama.

At least 37 records · Page 2Linked to original sources

PubMed2003

Inflammatory myoglandular colorectal polyps: a case series of nine patients.

Inflammatory myoglandular polyp is an uncommon benign colorectal polyp. We treated nine cases of histologically verified inflammatory myoglandular polyp. The polyps were identified as a pedunculated protrusion located in the distal part of the large intestine. On colonoscopy, eight polyps had a smooth, spherical, and hyperemic surface, accompanied by a patchy mucous exudate. Magnification endoscopy revealed a rugged surface composed of smooth nodules. These colonoscopic findings corresponded to hyperplastic glands with occasional cystic dilation and inflamed stroma with proliferation of smooth-muscle fibers. Inflammatory myoglandular polyp appears to be a distinctive clinical entity, with a unique appearance on colonoscopy.

Adult↗

PubMed2001

Reduced expression of hepatocyte growth factor activator inhibitor type-2/placental bikunin (HAI-2/PB) in human glioblastomas: implication for anti-invasive role of HAI-2/PB in glioblastoma cells.

Hepatocyte growth factor activator inhibitor type-2/placental bikunin (HAI-2/PB) is a serine proteinase inhibitor that contains 2 Kunitz-domains and a presumed transmembrane domain. It has broad inhibitory spectra against various serine proteinases showing potent inhibitory activities not only to hepatocyte growth factor activator but also to plasmin, trypsin and kallikreins. In this study, we investigated the expression of HAI-2/PB in human gliomas in vivo and the effects of HAI-2/PB on the fibrinolytic and invasive capabilities of human glioblastoma cells in vitro. With RNA blot analysis, HAI-2/PB mRNA was expressed in normal brain and in low-grade astrocytomas, but was hardly detectable in anaplastic astrocytomas and glioblastomas, indicating that its expression levels were inversely correlated with the histological grade of human gliomas. To further explore the possible role of HAI-2/PB in glioma progression, cultured human glioblastoma cell lines (U251 and YKG-1) were transiently transfected with an expression vector harboring human HAI-2/PB cDNA. Subsequent analysis indicated that the expression of HAI-2/PB suppressed the fibrinolytic activities of both glioblastoma cell lines. Moreover, HAI-2/PB inhibited Matrigel invasion of U251 and YKG-1 cells by 30% and 64%, respectively. This anti-invasive effect appeared to be mediated primarily by the inhibitory activity of HAI-2/PB against the serine proteinase-dependent matrix degradation. These findings suggest that the reduced expression of HAI-2/PB is possibly involved in the progression of human gliomas.

Astrocytoma↗

PubMed2001

Nondestructive quantification of neutral lipids by thin-layer chromatography and laser-fluorescent scanning: suitable methods for "lipidome" analysis.

A simple method for separation and quantification of neutral lipids was developed using thin-layer chromatography (TLC) and high-performance fluorescent scanning. Neutral lipid classes were separated using the double-developing TLC method and detected by rhodamine 6G and a laser-excited fluorescent scanner. The amount of lipids applied correlated with scanned intensity volume in a dose-dependent manner. The mass of each neutral lipid band was determined by comparing band intensities of unknown samples to dilution curves of authentic standards. After scanning the dye-sprayed TLC, acyl chain species of triglyceride (TG) extracted from TLC could be determined by gas chromatography. Using this method, we quantified the amounts of TG in mouse liver and found that the measured total mass of TG correlated with that obtained by enzymatic methods. Our method should provide the basic technique for "lipidome" analysis, designed to determine and compare total lipid classes and mass present in biological samples.

Animals↗

PubMed2001

3-hydroxy-3-methylglutaryl coenzyme A reductase is sterol-dependently cleaved by cathepsin L-type cysteine protease in the isolated endoplasmic reticulum.

We have recently shown that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an endoplasmic reticulum (ER) membrane protein, is degraded in ER membranes prepared from sterol pretreated cells and that such degradation is catalyzed by a cysteine protease within the reductase membrane domain. The use of various protease inhibitors suggested that degradation of HMG-CoA reductase in vitro is catalyzed by a cathepsin L-type cysteine protease. Purified ER contains E-64-sensitive cathepsin L activity whose inhibitor sensitivity was well matched to that of HMG-CoA reductase degradation in vitro. CLIK-148 (cathepsin L inhibitor) inhibited degradation of HMG-CoA reductase in vitro. Purified cathepsin L also efficiently cleaved HMG-CoA reductase in isolated ER preparations. To determine whether a cathepsin L-type cysteine protease is involved in sterol-regulated degradation of HMG-CoA reductase in vivo, we examined the effect of E-64d, a membrane-permeable cysteine protease inhibitor, in living cells. While lactacystin, a proteasome-specific inhibitor, inhibited sterol-dependent degradation of HMG-CoA reductase, E-64d failed to do so. In contrast, degradation of HMG-CoA reductase in sonicated cells was inhibited by E-64d, CLIK-148, and leupeptin but not by lactacystin. Our results indicate that HMG-CoA reductase is degraded by the proteasome under normal conditions in living cells and that it is cleaved by cathepsin L leaked from lysosomes during preparation of the ER, thus clarifying the apparently paradoxical in vivo and in vitro results. Cathepsin L-dependent proteolysis was observed to occur preferentially in sterol-pretreated cells, suggesting that sterol treatment results in conformational changes in HMG-CoA reductase that make it more susceptible to such cleavage.

Acetylcysteine↗

PubMed2001

Serial changes in signal intensities of the adjacent discs on T2-weighted sagittal images after surgical treatment of cervical spondylosis: anterior interbody fusion versus expansive laminoplasty.

BACKGROUND: There have been many reports about newly developed degenerative changes in the adjacent segments after anterior interbody fusion. It is a controversial issue whether the adjacent-segment disease in patients treated by anterior interbody fusion is the result of progressive cervical spondylosis at the adjacent levels or is caused by the arthrodesis. The aim of this study is to clarify the difference in postoperative effect on the adjacent segments between anterior interbody fusion and expansive laminoplasty. METHOD: This study included 14 patients who underwent pre- and postoperative MR images at 6 and 12 months. Seven patients underwent cervical interbody fusion and the other 7 patients underwent expansive laminoplasty. Disc degeneration was evaluated semiquantitatively by calculating the degenerative index (DI) that is a ratio of the intensity in the disc to that in the upper cervical cord. FINDINGS: In the anterior interbody fusion group, the adjacent disc intensities decreased within 12 months (F = 20.42; P < 0.01). The pre-operative mean DI was 0.59 +/- 0.16. The post-operative mean DIs were 0.56 +/- 0.16 at 6 months and 0.47 +/- 0.16 at 12 months. In the expansive laminoplasty group, the signal intensities of both the adjacent discs and the discs within the range of laminoplasty had no serial changes during the same period (F = 2.67; P = 0.09 and F = 0.15; P = 0.87 respectively). INTERPRETATION: Anterior interbody fusion had a significant influence on the adjacent discs even as soon as 12 months after surgery, but laminoplasty had no influence on them during the same period.

Adult↗

PubMed2001

A case of tacrolimus nephrotoxicity appearing in a second renal transplantation patient.

We experienced a case of a second renal transplantation patient. With the use of cyclosporin, he lost his first graft because of chronic rejection; with the use of tacrolimus, his second graft suffered from drug nephrotoxicity. On his second renal transplantation, his graft function deteriorated and required haemodialysis with the use of tacrolimus. Repeated biopsies did not reveal the typical characteristics of acute tacrolimus nephrotoxicity and acute rejection. His tacrolimus trough level was not high during the clinical course; however, by reducing tacrolimus dosage, his graft function eventually recovered to mild renal dysfunction. This observation was helpful for clinical diagnosis of the functional toxicity of tacrolimus. The case is interesting in considering the functional toxicity of tacrolimus and the difference between tacrolimus and cyclosporin in terms of immunosuppressive and nephrotoxic actions.

Biopsy↗

PubMed2001

Fluvastatin suppresses oxidative stress and fibrosis in the interstitium of mouse kidneys with unilateral ureteral obstruction.

BACKGROUND: Recently, we demonstrated increased oxidative stress in the interstitium of ureteral obstructed kidneys based on the increased expression of heme oxygenase-1 and immunohistochemical detection of advanced glycation end products (AGE) in the interstitium. Antioxidant therapy may have a therapeutic potential toward interstitial fibrosis of unilateral ureteral obstruction (UUO) kidneys. Fluvastatin is an HMG-CoA reductase inhibitor and has been demonstrated to have an antioxidant activity in vitro. METHODS: The effects of fluvastatin on UUO kidneys from the viewpoints of antioxidant action in vivo and antifibrosis action were studied. To investigate the antioxidant action and its therapeutic efficacy of fluvastatin in UUO kidneys, AGE accumulation and fibrosis in the obstructed kidneys was compared among vehicle-, pravastatin-, or fluvastatin-treated (10 or 40 mg/kg/day) groups. RESULTS: Tubulointerstitial fibrosis was significantly attenuated in fluvastatin-treated animals. Fluvastatin significantly suppressed the degree of immunostaining of AGE in UUO kidneys. CONCLUSIONS: These results provide evidence for the antioxidant action of fluvastatin in vivo. The decreased interstitial fibrosis along with a decreased oxidative stress marker in the interstitial lesion strongly suggests the existence of a causal relationship between them. Fluvastatin may have therapeutic value in slowing or preventing interstitial fibrosis in progressive renal disease.

Actins↗

PubMed2001

Development of composite cultured oral mucosa utilizing collagen sponge matrix and contracted collagen gel: a preliminary study for clinical applications.

A new type of cultured mucosa was developed as a mucosal substitute. This composite cultured oral mucosa (CCOM) was composed of (1) a lamina propria in which fibroblasts were embedded in contacted collagen gel and honeycomb structured collagen sponge and (2) stratified epithelial cell layers on the surface of the cultured lamina propria. CCOM had a well-stratified and differentiated epithelial cell layer, and its involucrin and laminin expression resembled that of normal oral mucosa. Desmosomes were recognizable with transmission electron microscopic examination. In the lamina propria, contracted collagen gel had pooled away from the sponge wall, leaving a sparse structure inside the collagen sponge. Transplantation of CCOM to nude mice was performed by creating full-thickness wound and then applying CCOM (n = 12). Murine skin allograft (n = 4) and no-graft conditions (n = 5) served as controls. The mice were sacrificed for histological evaluation and assessed for wound contraction 28 days after transplantation. The epithelium of the CCOM-treated group had five to 10 cell layers, and the dermis contained many fibroblasts and a large amount of collagen bundles. The wound contraction of the CCOM-treated group was statistically less than that of the no-graft group. These results indicate that CCOM has barrier functions against various stresses and can induce a fibrovascular ingrowth from the surrounding wound bed, and that CCOM could be applied in a clinical setting.

Animals↗

PubMed2001

A monoclonal antibody against bovine thrombin reacting to the C-terminal side of thrombin.

We succeeded in producing a monoclonal antibody (MAb) against bovine thrombin. The MAb belonged to mouse IgG(1), and its light chain consisted of kappa-chain. The MAb reacted with bovine and human thrombins, which were coated by coupling to poly-lysine-coated wells with glutaraldehyde, but did not react with the thrombin-like enzyme, habutobin. Furthermore, the MAb did not react with thrombin which was coated to plates without poly-lysine and glutaraldehyde. The concentration of thrombin in ovalbumin solution (10 mg/mL) could be measured by means of the enzyme-linked immunosorbent assay (ELISA) double sandwich method using the MAb and polyclonal antibody. Thrombin added to defibrinated plasma could not be detected by means of the ELISA double sandwich method using the present MAb, and this may be due to the AT-III activity in the defibrinated plasma. Postclotting thrombin could be detected by means of the ELISA-double sandwich method using the MAb. It is suggested, from the results of our experiments, that the MAb obtained reacted in a limited fashion to the C-terminal of bovine thrombin.

Animals↗

PubMed2001

Apoptosis induced by hypertonicity in Madin Darley canine kidney cells: protective effect of betaine.

BACKGROUND: In mammals, the renal medulla is in a hypertonic environment related to the renal concentrating mechanism. Renal cells accumulate osmolytes such as betaine to protect cells from the perturbing effect of high concentration of electrolytes. Hypertonicity-induced cell death and the effect of betaine were investigated in Madin Darby canine kidney (MDCK) cells. METHODS: Cell viability was detected by 3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyl tetrazolium bromide assay. DNA fragmentation was determined by FACS analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining and agarose gel electrophoresis. Activities of caspase-1, -3, -8, and -9 were measured. RESULT: When the cells were exposed to 700 mOsm medium for 24 h, 40% of the cells were detached. TUNEL staining showed that about 20% of detached cells were apoptotic, indicating that both necrosis and apoptosis contributed to the hypertonicity-induced cell death in MDCK cells. DNA laddering was demonstrated in hypertonic cells. Caspase-3, -8, and -9 activities of the adherent cells exposed to 700 mOsm for 24 h increased approximately 20-, 3-, and 4-fold the value of isotonic cells, respectively. However, there was no significant change in caspase-1 activity. Addition of 1 mM betaine into the medium protected the cells against the hypertonicity-induced cytotoxicity and apoptosis. Betaine prevented the induction of caspase-3, -8, and -9 activities after hypertonic exposure to about 50%. CONCLUSIONS: The present study demonstrates that (i) apoptosis is involved in the hypertonicity-induced cell death in MDCK cells; (ii) caspase-3, -8, and -9 may contribute to the apoptosis; and (iii) betaine has protective effect on the hypertonicity-induced apoptosis.

Animals↗

PubMed2001

Identification of cyclophilin as an IgE-binding protein from carrots.

BACKGROUND: Plant food allergies have been associated with pollenosis, although most of the causative allergens are as yet undefined. It is important to elucidate the properties of plant food allergens in order to minimize a patient's risks in food selection. The purpose of the present study was to examine and characterize the IgE-binding proteins in carrots as possible allergens by using patients' sera. METHOD: IgE-binding proteins in carrot extract were screened by an immunoblot technique using sera of patients with atopic dermatitis (selected based upon a case history of food allergies). An allergenic protein was purified from carrot extract by chromatographic procedures. The N-terminal amino acid sequence of allergenic protein was determined and subjected to a computer homology search. Cross-reactivity between carrot and birch allergens was examined by immunoblotting. RESULTS AND CONCLUSION: A unique, approximately 20-kDa allergenic protein that reacted with about 14% of patients' sera was isolated and characterized. The N-terminal amino acid sequence of the purified protein was found to be homologous with those of plant cyclophilins. This allergen exhibited a peptidyl-prolyl cistrans isomerase activity, which was inhibited by the conjugation of cyclosporin A. These properties of the allergenic protein isolated from carrot identified it as a cyclophilin, a possible plant food allergen. No cross-reactivity between this 20-kDa carrot allergen and Bet v 7, a birch pollen cylcophilin, was observed.

Adolescent↗

PubMed2001

Expression of adrenomedullin by human placental cytotrophoblasts and choriocarcinoma JAr cells.

Adrenomedullin is a multifunctional peptide expressed in a variety of tissues. This study was conducted to investigate the expression of adrenomedullin and its mRNA by human trophoblasts and the possible existence of adrenomedullin receptor in those cells. Human placentas in all three trimesters were obtained from patients undergoing therapeutic abortions and deliveries. Total RNA was extracted from placental trophoblastic tissues and JAr choriocarcinoma cells, and the expression of adrenomedullin mRNA was determined by RT-PCR. Immunohistochemical analysis was performed by the avidin/biotin immunoperoxidase method using a specific antibody to adrenomedullin. The secretion of adrenomedullin by JAr cells cultured in medium containing [35S]cysteine-[35S]methionine was determined by immunoprecipitation followed by PAGE. The presence of adrenomedullin receptor in JAr cells was examined using a binding assay with [125I]rat adrenomedullin. Adrenomedullin mRNA was expressed by human placental trophoblastic tissues in all three trimesters and by JAr cells. Immunohistochemical analysis revealed that adrenomedullin is expressed by cytotrophoblasts in placentas in all three trimesters, but not by syncytiotrophoblasts. The expression of adrenomedullin in the cytotrophoblast was most abundant in first trimester placenta and became less abundant during the course of pregnancy. JAr cells synthesized and secreted immunoreactive adrenomedullin. Binding assay with [125I]rat adrenomedullin demonstrated specific binding of adrenomedullin to JAr cells, indicating the existence of a specific receptor for adrenomedullin in trophoblastic cells. Adrenomedullin is transcribed and secreted by cytotrophoblastic cells that possess adrenomedullin receptor. Adrenomedullin may play a potential role as an autocrine/paracrine factor in the growth of cytotrophoblasts, especially in early gestation.

Adrenomedullin↗

PubMed2001

Effects of shifts up and down in osmotic pressure on production of tissue plasminogen activator by Chinese hamster ovary cells in suspension.

The effects of changes in osmotic pressure on the production of tissue plasminogen activator (tPA) by Chinese hamster ovary (CHO) cells in suspension were investigated. The osmotic pressure was shifted up from 300 mOsm/kg and down from 400 or 500 mOsm/kg to 400, 350, or 300 mOsm/kg during the cell growth and tPA production phases. In both phases, the specific cell growth rate was higher at a lower osmotic pressure after the shift, whatever it was up or down. After the osmotic pressure was shifted up during the production phase, the specific tPA production rate was high at a high osmotic pressure; however, shifting the osmotic pressure down also resulted in a high specific rate of tPA production. Additionally, specific production rate increased for 2 d after upward or downward shifts during the growth phase. Shifting the osmotic pressure cyclically between 300 and 500 mOsm/kg during the production phase improved the tPA production 1.13-fold compared with the amount produced at a constant osmotic pressure of 300 mOsm/kg.

Journal Article↗

PubMed2001

[Gene therapy and tissue engineering in nephrology and renal transplantation].

Human genome project will be completed in 2003 and we will soon obtain the information of the whole DNA sequence of the human genome. This should affect the therapy of progressive renal diseases since we have no effective remedy to cure the renal diseases. Gene therapy, renal engineering and generation of new drug can be achieved by using the information of human genome. In this context, we described our recent endeavors concerning the gene therapy of transplant kidney, seeking the renal stem cells and reprogramming factors, and exploring genes related to renal fibrosis. Completion of bioinformatics, can facilitate the above post-genome project.

Animals↗

PubMed2001

[The histological antitumor effect and side effects of preoperative chemotherapy for patients with oral squamous cell carcinoma--comparison between low-dose and high-dose CDDP regimens].

Preoperative chemotherapy should be effective against cancers and have few side effects that would prevent surgery. We investigated the histological effects and side effects of low- and high-dose CDDP chemotherapy against oral squamous cell carcinoma (SCC), and discuss the therapeutic benefits of each regimen. Thirty-six patients were divided into two groups as follows, in a non-randomized manner: A) low-dose CDDP (17 patients): CDDP 5 mg/m2/day + UFT 400 mg/day (day 1-5) (1 or 2 courses), B) high-dose CDDP (19 patients): CDDP 70-100 mg/m2/day (day 1) + peplomycin 5 mg/day (day 2-6) (1 or 2 courses). Curative surgery was conducted 1 week after protocol A or 2-3 weeks after protocol B. The histological antitumor effects were evaluated with Ohboshi & Shimosato's classification using surgical materials of primary tumors. In this classification, grade IIB, III and IV were as effective. Maximum histological effect was seen with grade IIB for regimen A and grade IV for regimen B. Four of 17 patients (23.5%) responded to regimen A and 13 of 19 patients (68.4%) to regimen B. Side effects, such as nausea, vomiting and myelosuppression, appeared with regimen B, but were seen little with regimen A. The 2-year survival rate was 93.3% with regimen A and 78.9% with regimen B. With regimen A, the 2-year survival rate of effective cases was 100% and that of ineffective cases was 91.7%. With regimen B, the rate was 92.3% and 50.0%, respectively. Effective cases showed good prognosis in both groups. The low-dose CDDP regimen was not so effective against primary tumors histologically, but the prognosis was good. The low-dose CDDP regimen appears to be useful for preoperative chemotherapy of oral SCC.

Antibiotics, Antineoplastic↗

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) (6)--Six-month repeated oral dose toxicity study in dogs].

A six-month repeated oral dose toxicity study of Cefmatilen hydrochloride hydrate (S-1090) at dose levels of 40, 100 and 250 mg potency/kg/day was conducted in male and female beagle dogs. No toxicologically significant changes were observed in general conditions of all animals. Reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet) were observed in all treated groups. Plasma irons showed a tendency to increase in the males and females of the 250 mg potency/kg group. However, as no changes suggesting anemia or hepatic injury were observed in this group, the change of plasma iron was considered to have no toxicological significance. No toxicologically significant changes were observed in other examination items. The plasma S-1090 concentrations increased in a manner less than dose-proportional. Based on the above results, the NOAEL of S-1090 was assessed to be 250 mg potency/kg/day.

Administration, Oral↗

PubMed2001

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (3)--One- and three-month repeated oral dose toxicity studies in rats].

One- or three-month repeated oral dose toxicity studies of Cefmatilen hydrochloride hydrate (S-1090) in rats were conducted. Doses were set at 80, 200, 500 and 1250 mg potency/kg/day in the one-month toxicity study, and 100, 300 and 1000 mg potency/kg/day in the three-month toxicity study. Body weights increased favorably and no deaths occurred in all treated groups of both studies. The changes observed in both studies were soft feces, abdominal distention, increased food and water consumption, decreases of urine volume and pH, and a decrease of blood neutrophils in almost all treated groups, reddish-brown feces (due to chelated products of S-1090 and its decomposition products with Fe3+ in the diet) in groups dosed at 300 mg potency/kg or more, and a lower mature granulocyte ratio in the bone marrow in groups dosed at 1000 mg potency/kg or more. In necropsy, cecal enlargement with a large amount of muddy content was observed in all treated groups of both studies. In the three-month toxicity study, elevated drug-metabolizing enzyme activities were noted in the liver of the males in the 1000 mg potency/kg group. These changes were slight except for the cecal enlargement and the rats recovered well with drug withdrawal. Since no toxicologically significant changes were noted in either study, the NOAEL of S-1090 was estimated to be 1250 mg potency/kg/day in the one-month toxicity study and 1000 mg potency/kg/day in the three-month toxicity study.

Administration, Oral↗