Search PubMed⌕ Search

Biomedical subjects

T Yamamura

Publications and source records attributed to T Yamamura.

At least 145 records · Page 8Linked to original sources

Long-term effects of small bowel transplantation on intestinal motility.

We previously found that the contractile motility of the jejunum was increased 4 weeks after transplantation, and that the dominant intrinsic neural component was changed from cholinergic to nonadrenergic, noncholinergic (NANC). The present study investigated the long-term effects of transplantation on jejunal motility using rats that survived for 2 years after surgery. Jejunal strips were harvested from various groups of rats, and intestinal motility was assessed by electrical transmural stimulation. Stimulation produced a similar increase of contraction at 4 weeks and 2 years after grafting. Pretreatment with atropine showed that the cholinergic component of contraction was 45%, 24%, 32%, and 24% in controls, rats 4 weeks after transplantation, 2-year-old controls, and rats 2 years after transplantation, respectively. The NANC component (obtained with atropine and guanethidine) in each group was, respectively, 56%, 73%, 60%, and 69%. The actual value of the tetrodotoxin-insensitive myogenic component was significantly increased at 2 years after transplantation. A substance P antagonist ([Arg6, D-Trp7,9, Mephe8], substance P 6-11), inhibited most of the NANC contraction after transplantation. These results suggested that substance P has a key role in the motility of transplanted small bowel throughout the life of the grafts.

Analgesics↗

Demonstration of interleukin-3 receptor-associated antigen in the central nervous system.

We previously reported that interleukin-3 (IL-3) acts as a neurotrophic factor for cholinergic neurons. However, it has not yet been determined whether the action is derived from the interaction of IL-3 with IL-3 receptors. As the first step to study IL-3 receptors in the central nervous system, we examined the presence and localization of IL-3 receptor-associated antigen (IL-3RAA) in mouse and rat brain. Immunohistochemically, IL-3RAA, which is closely involved both in the IL-3 binding to IL-3 receptors and the tyrosine phosphorylation in the signal transduction for IL-3 in hematopoietic cells, was demonstrated in neurons throughout the brain. This was confirmed in primary cultured neurons and neuronal cell lines by immunocytochemistry and flow cytometry. The staining intensity varied among regions and the most intense immunoreactivity for IL-3RAA was found in large neurons in the magnocellular basal nuclei, pyramidal cells in the cerebral cortex, and neuronal cells in some nuclei of the brainstem. Not only cholinergic cell lines derived from the septal region but also other neuronal cell lines exhibited IL-3RAA immunoreactivity by flow cytometry. Therefore, we conclude that IL-3RAA is present in a wide variety of neurons in the brain including cholinergic neurons of the basal forebrain. Western blot analysis revealed that the candidates for IL-3RAA are 145, 100, and 50 kDa proteins both in neuronal and IL-3-dependent cell lines.

Animals↗

Subtypes of endothelin ETA and ETB receptors mediating tracheal smooth muscle contraction.

In the isolated rabbit trachea, endothelin (ET)-1, ET-3 and the selective ETB receptor agonists, IRL 1620 and sarafotoxin S6c (STXc), induced contraction with EC50 of 2-9 nM. An ETA1 receptor antagonist, BQ-123, was ineffective whereas desensitization of the ETB receptor strongly antagonized the effect of ET-3, IRL 1620 and STXc. An ETB1 receptor antagonist, RES-701-1, antagonized the effects of ET-3 and IRL 1620 whereas the effect of STXc was antagonized by an ETB2 receptor antagonist, BQ-788. In the ETB-desensitized trachea, only ET-1 induced large contraction that was partially antagonized by BQ-123. These results suggest that ET induces tracheal contraction by activating multiple ET receptors: the ET-1-selective ETA (BQ-123-sensitive ETA1 and insensitive ETA2 subtypes) and the isopeptide-nonselective ETB receptors (RES-701-1-sensitive ETB1 and insensitive ETB2 subtypes).

Animals↗

Polymorphic reticulosis is a neoplasm of large granular lymphocytes with CD3+ phenotype.

BACKGROUND: Polymorphic reticulosis, a type of lethal midline granuloma (LMG), has been referred to as nasal T-cell lymphoma (NTL) because of its proliferating cells' positive reactivity to anti-T-lymphocyte antibodies. Recently, several studies have suggested that proliferating cells in NTL may be natural killer (NK) in nature. NK cells and human nonmajor histocompatibility-restricted cytotoxic T-lymphocytes have the morphology of large granular lymphocytes (LGL) (i.e., a high cytoplasmic:nuclear ratio and cytoplasmic granules). Whether NTL-LMG possesses an LGL morphology is examined in this study. METHODS: Two lymph node smears, peripheral blood showing a leukemic picture, and an electron microscope (EM) examination of a cutaneous lesion, respectively, were obtained from four patients with NTL-LMG. Immunohistochemical examination of the proliferating cells and of the Epstein-Barr virus (EBV) genome by both polymerase chain reaction and in situ hybridization also were performed. RESULTS: All patients presented with necrotic and granulomatous lesions in the upper respiratory tract. Histology showed polymorphous cellular infiltrates containing large atypical cells with positive reaction to CD3 (three patients), CD43 (two patients), CD45RO (two patients), and OPD4 (one patient). Imprint smears revealed azurophilic large membrane-delimited granules in an ample cytoplasm, which was confirmed by EM. The presence of the EBV genome in the tumor cells was observed in one patient. CONCLUSION: The current findings showed that NTL-LMG or polymorphic reticulosis is a proliferation of LGL with a CD3+ phenotype.

Adult↗

Water and electrolyte balance after ileal J pouch-anal anastomosis in ulcerative colitis and familial adenomatous polyposis.

The water and electrolyte balance was studied in 31 patients with ulcerative colitis (UC) and 22 with familial adenomatous polyposis (FAP) who underwent staged surgery involving colectomy and ileal J pouch-anal anastomosis (IAA), preoperatively, after terminal ileostomy, after high ileostomy, and after ileostomy closure. Serum electrolytes did not differ between each surgical stage. After terminal or high ileostomy, daily urine volume and urinary sodium loss was significantly lower, and daily fecal weight and fecal sodium loss was significantly higher than preoperatively. After ileostomy closure, urinary and fecal sodium loss became closer to preoperative value. Daily urinary potassium loss was significantly higher and fecal loss was lower after terminal and high ileostomy than preoperatively and did not show a significant change after ileostomy closure. The urinary sodium to potassium ratio after ileostomy closure was lower than preoperatively, but was higher than that after terminal and high ileostomy. Plasma aldosterone and renin levels were only significantly increased after high ileostomy. These findings indicate that high or terminal ileostomy caused chronic dehydration, which was compensated for by activation of the renin-aldosterone axis, while the water and electrolyte balance became closer to normal after ileostomy closure following ileoanal anastomosis.

Adenomatous Polyposis Coli↗

Genetic but not diet-induced hypercholesterolemia causes low apolipoprotein A-IV level in rabbit sera.

The present report describes a competitive enzyme immunoassay for rabbit apolipoprotein A-IV (apo A-IV). This assay was applied to the determination of its concentration and distribution in sera from normolipidemic and hyperlipidemic rabbits. The assay was sufficiently sensitive to study this 42-kDa protein in lipoproteins fractionated from 200 microliters of serum by FPLC gel filtration. In normolipidemic sera (n = 8), apo A-IV concentration was 5.32 +/- 0.76 mg/dl. A diet rich in cholesterol (0.5%), which induced an 18-fold increase in serum cholesterol, did not significantly alter apo A-IV concentration (6.65 +/- 1.52 mg/dl, n = 8). By contrast, genetically induced hypercholesterolemia (Watanabe heritable hyperlipidemia, WHHL mutation) caused a significantly reduced level of apo A-IV (3.8 +/- 1.14 mg/dl, n = 7). In each of the groups studied, apo A-IV was distributed in two distinct pools; a high-density lipoprotein-(HDL) associated pool and a lipoprotein-free pool. However, compared to normal, the distribution of apo A-IV in WHHL rabbit sera was shifted towards the lipoprotein-free pool. Consistent with previously reported observations on apo A-I, these results are compatible with the hypothesis of an impaired reverse transport of cholesterol in WHHL rabbits, an animal model for familial hypercholesterolemia.

Amino Acid Sequence↗

Exogenous supply of artificial lipoproteins does not decrease susceptibility to atherosclerosis in cholesterol-fed rabbits.

We investigated the effects of reconstituted apo A-I-containing high-density lipoprotein (r-HDL, homologous to small pre-beta-migrating HDL) and reconstituted triglyceride-rich lipoprotein (r-TRL, a mixture of Intralipid and apo E) on atherogenesis in rabbits fed a 0.5% cholesterol diet for 8 weeks. Male Japanese white rabbits (n = 17) were divided into three groups: the control group (n = 7) received a placebo and 2.5 ml of Intralipid 20 h later; the second group (n = 6) received r-HDL containing 18 mg of apo A-I followed by 2.5 ml of Intralipid; and the third group (n = 4) received 18 mg of r-HDL and 2.5 ml of r-TRL containing 4 mg of apo E. Rabbits were injected with the agents weekly and the same interval (20 h) was maintained between the two injections. Three minutes after the injection of r-HDL, a sharp increase in the pre-beta-migrating fraction was observed. The cholesterol-rich diet similarly increased serum lipids in the three groups. No significant changes of the HDL cholesterol and apo A-I concentrations were observed in the three groups. Conversely, there was a 12-fold increase of apo E which correlated positively with the total cholesterol level. Injection of r-HDL and r-TRL caused slight inhibition of fatty streak development and lipid deposition in the aortic wall, but neither change was statistically significant. Lipid accumulation in the liver was similar in all three groups. These results suggest that the physiological properties of artificial and native lipoproteins may differ.

Animals↗

Analysis of proteolipid protein (PLP)-specific T cells in multiple sclerosis: identification of PLP 95-116 as an HLA-DR2,w15-associated determinant.

Multiple sclerosis (MS) is a putative autoimmune disease that is linked with HLA-DR2,w15. Proteolipid protein (PLP) is a candidate autoantigen in MS, but the disease-associated epitopes have not been determined. Using overlapping and non-overlapping PLP peptides, we have studied the T cell response to the major hydrophilic domain PLP 85-159 in the peripheral blood of MS and healthy subjects (HS). Short-term T cell lines (TCL) were selected against each peptide using microwell plates and the frequency of peptide-specific TCL was estimated. PLP 95-116-specific TCL were most efficiently generated and the frequency was significantly higher in MS compared with HS (P < 0.05). When compared between DR2,w15+ and DR2,w15- MS, TCL frequency to PLP 95-116 was significantly higher in DR2,w15+ MS (P < 0.005) and TCL reactive to the overlapping peptide 105-124 were also increased in DR2,w15+ MS (P < 0.025). Using DR gene-transfected L cells, we could show that the DRB1*1501 product of the DR2 haplotype presents PLP 95-116 to TCL selected against the peptide. These results imply that PLP 95-116 represents a major epitope for the DR2,w15+ MS.

Adult↗

Evaluation of lens transparency changes through photographed images during a 13-month observation period.

Since the development of the anterior eye segment analysis system, several new types of anterior eye segment biometry have been performed. The main aim of this study was to evaluate whether changes in cataractous progression or an increase in lens transparency loss are detectable during a relatively short period of 13 months by measuring the intrapupillary opaque shadow area through retroillumination images or by calculating the light scattering intensity at the deepest cortical layer of the lens through Scheimpflug slit images. Secondly, the relationship between maximally dilated pupil sizes and patients' ages and that between cases with and without diabetes were studied. Thirty-one eyes (49.2%) of sixty-three cataractous lenses showed more than 5% increase in the opaque shadow area. Forty-five eyes (60.0%) showed more than a 5% increase in light scattering intensity. 92.5% of diabetic eyes and 92.3% of nondiabetic eyes showed pupil sizes over 6.5 mm after an instillation of mydriatica. In our study the applied method guaranteed a high reproducibility; thus is might be possible to detect an increase in cataractous changes and lens transparancy in around 50% of examined subjects in a period as short a 1 year. For the evaluation of cataract progression through a retroillumination image, the recommendable pupil size is > or = 6.5 mm.

Aged↗

Common mutations in the low-density-lipoprotein-receptor gene causing familial hypercholesterolemia in the Japanese population.

Familial hypercholesterolemia (FH) is a common genetic disorder caused by mutations of the LDL-receptor gene. In the present study, we investigated four Japanese FH homozygotes and identified five point mutations: a splice site mutation in intron 12 (the 1845 + 2 T-->C mutation), a missense mutation in exon 7 (the C317S mutation), a nonsense mutation in exon 17 (the K790X mutation), a missense mutation in exon 14 (the P664L mutation), and a missense mutation in exon 4 (the E119K mutation). We developed simple methods for detecting these mutations. When we examined the presence of these mutations in 24 unrelated FH homozygotes, the 1845 + 2 T-->C mutation was found in 7 of them, and the other four mutations were unique for each proband. We also screened 120 unrelated FH heterozygotes for these mutations and found that the frequencies of the 1845 + 2 T-->C, C317S, K790X, P664L, and E119K mutations were 13.3% (16/120), 6.7% (8/120), 6.7% (8/120), 3.3% (4/120), and 1.7% (2/120), respectively. These mutations were found in more than 30% of unrelated Japanese FH patients. By using the detection methods developed in this study, the diagnosis of more than 30% of the genetic bases of Japanese FH heterozygotes is expected.

Adult↗

Effects of adriamycin, an anticancer drug showing testicular toxicity, on fertility in male rats.

Adriamycin (ADR), an anticancer drug,was intravenously administered to Slc:SD male rats at doses of 0, 1 and 2 mg/kg once a week for 4 or 9 weeks before pairing, and the treatment period and parameters suitable for detection of male fertility disorder were examined. No adverse effects were observed on the copulation index, fertility index and spermatozoa, but testicular weights were low in the 1 and 2 mg/kg groups after 4-week treatment. In the 2 mg/kg group after 9-week treatment, 11 of 12 males had died or became moribund, and no successful pregnancies were observed. The males in the 1 and 2 mg/kg groups after 9-week treatment had decreased weights of the genital organs, an extremely decreased number of sperm and low sperm motility as well as a low implantation rate and a decreased number of live fetuses. Microscopically, the numbers of spermatogonia were decreased in the 1 and 2 mg/kg groups after 4-week treatment, whereas the numbers of even spermatozoa were diminished and genital organs showed atrophy after 9-week treatment. These results indicate that 4-week treatment before pairing is sufficient to detect effects of ADR on the testis, especially on spermatogonia, and that microscopic findings and testis weight are appropriate parameters for detection of male fertility disorders.

Animals↗

[Pharmacokinetic study in biochemical modulation therapy of UFT with leucovorin tablet].

Preoperative oral treatment with UFT and leucovorin tablet was performed. Pharmacokinetics, degree of degeneration in the tumor tissue and side effects were studied in 34 patients with colorectal cancer preoperatively given 400 mg/day of UFT with 20 mg/day of leucovorin tablet or 400 mg/day of UFT alone. Results were as follows; 1) there was no significant difference between UFTL group and UFT group regarding concentration of FdUMP in the tumor tissue. In UFTL group, concentration of FdUMP was higher in the tumor tissue of moderately differentiated adenocarcinoma than that of well differentiated adenocarcinoma. No significant differences regarding concentration of FdUMP were obtained between diploid and aneuploid groups. 2) TS inhibition rate in the tumor tissue was 66.8% in UFTL group and 53.2% in UFT group, and there was a significant difference between these two groups. TS inhibition rate in the tumor tissue was higher than that in the normal tissue either in UFTL group or UFT group. However, there were no significant differences of TS inhibition rates regarding differentiation of tumor tissue or DNA ploidy pattern. 3) Degree of degeneration of more than Grade 2 was not obtained in any patients of either UFTL or UFT group. 4) There was no change in blood laboratory data between before and after medication. Only one patient complained Grade 1 pruritus in UFTL group. These results suggest that oral biochemical modulation therapy of UFT with leucovorin tablet is effective because of pharmacokinetically high anti-tumor effect and minimal side effects.

Adenocarcinoma↗

Ileoanal anastomosis and ileoanal canal anastomosis in Japan: comparative retrospective study.

A questionnaire survey of ten institutions in Japan revealed that restorative proctocolectomy accounted for 81.8% of the surgical procedures performed in patients with UC in the last 5 years (1989-1993); ileoanal anastomosis (IAA) and ileo-anal canal anastomosis (IACA) were performed in 63% and 33% of these patients, respectively. Comparison of the two series showed that IACA was technically simpler and yielded better continence, but that it entailed a potential risk of recurrence of the disease in the remaining anal canal mucosa. Although IACA seems to be a useful surgical option for UC, until the long-term outcome of the procedure can be elucidated. It may be better regarded as a very low variation of IRA rather than as an improved technical version of IAA.

Adult↗

Changes of intestinal motility after small bowel transplantation in the rat.

Small bowel transplantation disturbs the enteric neural network as a result of complete extrinsic denervation, but few data are available on the status of the intrinsic neurons in intestinal grafts. This study assessed intestinal motility and the intrinsic innervation of jejunal longitudinal muscle after transplantation in rats using electrical transmural stimulation. Syngeneic total small bowel transplantation was performed in male Lewis rats using microsurgical techniques. The rats were divided into four groups-i.e., a control group and groups examined at one (G1), two (G2), and four (G4) weeks after transplantation. Jejunal strips were mounted in a superfusion apparatus for examination. Functional innervation was assessed by comparing contraction and relaxation following stimulation at 10 Hz with or without various drugs. All grafts showed increased contractile motility when compared with the control group. The cholinergic excitatory components in the control, G1, G2, and G4 groups were 45%, 73%, 66%, and 24%, respectively, while nonadrenergic noncholinergic-excitatory components were 56%, 53%, 57%, and 78%. Thus, there was a marked change in excitatory innervation after transplantation. However, the tetrodotoxin-insensitive (myogenic) component showed no changes in active tone after transplantation. Adrenoceptor antagonists had a decreased effect on all grafts except for yohimbine (an alpha 2 blocker). The contractile motility of transplanted jejunum was increased compared with that of the control bowel. However, the dominant intrinsic component varied with the time after transplantation.

Adrenergic alpha-Antagonists↗

HSP72 induction by heat stress is not universal in mammalian neural cell lines.

Heat-induced expression of 72-kDa heat shock protein (HSP72) was investigated in a panel of neuronal and non-neuronal cell lines by immunoblotting and immunocytochemistry using monoclonal antibodies directed to HSP72. By immunoblotting, HSP72 expression was observed in most cell lines of mouse (SN6.1b, CL8c4.7, NSC34.6, B2A, C2C12), rat (PC12, C-6, L3), and human (NB-1, GOTO, IMR-32, HeLa) origin under the heat-stressed condition. The mouse neuroblastoma cell line N18TG2, however, did not express HSP72 under the heat-stressed condition. By immunocytochemistry, HSP72 was undetectable in the heat-stressed N18TG2 cells, while it was identified in the heat-stressed SN6.1b cells, a clonal hybrid neuron between N18TG2 and mouse septal cholinergic neuron. By exposure to a priming sublethal heat shock, SN6.1b cells but not N18TG2 cells acquired a significant level of tolerance to a subsequent lethal heat shock. These results suggest that heat-induced expression of HSP72 may contribute to acquisition of the thermotolerant state in SN6.1b cells.

Animals↗