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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 235 records · Page 13Linked to original sources
PubMed1998

Preparation of difluoro analogs of CCGs and their pharmacological evaluations.

All the stereoisomers of 2-(2-carboxy-3,3-difluorocyclopropyl)glycines (F2CCGs) were synthesized in enantiomerically pure forms using (R)-2,3-O-isopropyl-ideneglyceraldehyde as a chiral precursor. L-F2CCG-I, one of the stereoisomers corresponding to an extended form of L-glutamate was found to be a potent agonist for metabotropic glutamate receptors (mGluRs).

Amino Acids, Dicarboxylic↗
PubMed1998

Correlation between spinal cord compression and abnormal patterns of median nerve somatosensory evoked potentials in compressive cervical myelopathy: comparison of surface and epidurally recorded responses.

To investigate the correlation between the level of spinal cord lesion and the abnormal pattern of median nerve somatosensory evoked potentials (SSEPs), evoked spinal cord potentials (ESCPs) were also recorded from the posterior epidural space intraoperatively in 18 patients with compressive cervical myelopathy. Levels of symptomatic spinal cord compression were determined by ESCP findings. Spinal N13 potential of the SSEPs was recorded from the surface of the posterior neck with anterior neck reference. Brainstem P14 and cortical N20 potential were recorded from the parietal scalp contralateral to the stimulated side. Spinal N13, P14, and N20 potentials were all normal when the ESCPs were abnormal at localized segmental region (C4-5 or C5-6 level alone). Spinal N13 potential was significantly attenuated in all of patients with abnormal ESCP findings at widespread segmental area of the median nerve territory. In four of these seven patients, brainstem P14 potential was also prolonged or diminished, but three patients showed normal P14 and N20 potentials. Isolated P14 abnormality with normal spinal N13 potential was characteristic in patients with abnormal ESCP at the C3-4 lesion. Although sensitivity of abnormal ESCP was higher than that of the SSEPs, abnormal patterns of spinal N13, P14 and N20 potentials following median nerve stimulation were useful in detecting not only the pathology (posterior horn and/or posterior column) but also symptomatic spinal compression level in compressive cervical myelopathy.

Adult↗
PubMed1998

In vivo formation of a Schiff base of aminoguanidine with pyridoxal phosphate.

Aminoguanidine (AG) is considered to be a promising compound for the treatment of diabetic complications. We examined the in vitro and in vivo formation of Schiff bases of AG with pyridoxal 5'-phosphate (PLP) and pyridoxal (PL). AG reacted in vitro far more rapidly with PLP to form a Schiff base (PLP-AG) than with PL to form another Schiff base (PL-AG). Administration of AG at 7 mM in drinking water for 18 weeks caused the formation of PLP-AG in the liver and kidney of mice (12.1 +/- 1.6 and 3.8 +/- 0.64 nmol/g of tissue, respectively, mean +/- SD, N = 6). The amount of PLP in the liver of mice AG administered was significantly lower than that of control mice (4.0 +/- 1.4 vs 17.4 +/- 1.3 nmol/g of wet tissue, mean +/- SD, N = 6). Simultaneous administration of pyridoxine (1 mM in drinking water) with AG (7 mM in drinking water) did not ameliorate the decrease in tissue PLP and caused the excess formation of PLP-AG. The results suggest that attention should be paid to the deficiency of tissue PLP in the clinical use of AG.

Animals↗
PubMed1998

The hydroxyl radical scavenger Nicaraven inhibits glutamate release after spinal injury in rats.

Neuronal degeneration after trauma is mediated in part by release of excitatory amino acids (EAAs) and oxygen free radicals (OFR). We evaluated the effect of i.v. treatment with a hydroxyl radical scavenger ((+/-)-N,N'-propylenedinicotinamide; AVS) and spinal hypothermia (33 degrees C) on spinal CSF glutamate release after spinal trauma. In a control group, spinal compression evoked at 10 min a significant increase (5-fold) in glutamate which declined over 4 h (2.1-fold). AVS treatment attenuated glutamate release but had no additive effect. These data suggest that this compound can be effective in modulating spinal excitotoxicity resulting from increased OFR synthesis and corresponding potentiation of EAA release.

Animals↗
PubMed1998

Effect of a 3'-->5' exonuclease with a proofreading function on the fidelity of error-prone DNA polymerase alpha from regenerating liver of aged rats.

A nuclease that releases noncomplementary nucleotides from the 3'-end of DNA was isolated and highly purified from rat liver extract. The d(T9-C) priming activities for DNA synthesis in vitro by DNA polymerases alpha and beta were recovered by the addition of this enzyme, which itself does not contain a DNA polymerase activity. This nuclease hydrolysed nucleotides from the 3'-end, but did not remove [32P]-labeled nucleotides from the 5'-terminus of specifically labeled DNA. Also, the reaction products released from the 3'-end of DNA were all mononucleotides. These results indicate that the exonuclease is a 3'-->5' exonuclease with properties the same as those of DNase VII from human placenta. Rat DNase VII requires 4 mM MgCl2 or 0.125 mM MnCl2 for maximum activity, and shows a pH optimum of 7.5. These optimal conditions are similar to those of DNA polymerases, and indicate that both rat DNase VII and DNA polymerases are able to act under same conditions. Non-complementary nucleotide incorporation by DNA polymerase alpha from aged rat has been observed during in vitro DNA synthesis on poly dA-dT10. The amount of this mis-incorporation is decreased by the coexistence of the 3'-->5' exonuclease, but not all errors are edited out. Thus, this rat DNase VII is suggested to play an important role in proofreading during DNA synthesis.

Aging↗
PubMed1998

Bleomycin-induced pulmonary fibrosis in rat is associated with increased expression of collagen-binding heat shock protein (HSP) 47.

Increased accumulation of collagens in extracellular matrix (ECM) is mainly responsible for bleomycin-induced pulmonary fibrosis in rats. This study was designed to assess whether increased collagen accumulation in bleomycin-induced pulmonary fibrosis is associated with heat shock protein (HSP) 47, a molecular chaperone for collagen biosynthesis. We investigated the expression of type I and type III collagens and HSP47 in bleomycin-induced pulmonary fibrosis. Fifteen male Wistar rats were divided into two groups; group I: bleomycin-induced pulmonary fibrosis; group II: PBS-treated age-matched control rats. Pulmonary fibrosis was induced by injecting a single dose of bleomycin sulphate (5 U/kg body weight) intratracheally. Three bleomycin-treated rats and two age-matched control rats were sacrificed at the end of each of the 1st, 2nd and 4th weeks of the experiment. In bleomycin-treated rats, histological examination revealed pulmonary fibrosis, which increased with time. Increased type I and type III collagen desposition was observed in the lungs of all the bleomycin-treated rats. Weak immunostaining of HSP47 was noted in the control lungs. In contrast, strong immunostaining for HSP47 was seen in all the bleomycin-treated fibrotic lungs. In addition, increased numbers of phenotypically altered myofibroblasts (alpha-smooth muscle actin immunopositive) and fibroblast (vimentin immunopositive) were seen in bleomycin-treated lungs and found to express HSP47. Parallel increase of collagens and their molecular chaperone HSP47 expression was found in the bleomycin-treated lungs, and their co-localization could be detected by double immunostaining. Overexpression of HSP47 may play a significant part in the excessive assembly of collagens and could contribute in this way to the fibrosis found in bleomycin-treated rat lungs.

Animals↗
PubMed1998

Age-related nephropathy in the Fischer 344 rat is associated with overexpression of collagens and collagen-binding heat shock protein 47.

To explore the possible role of heat shock protein (HSP) 47 in the age-related renal changes in Fischer 344 (F 344) rats, the expression of collagen-binding HSP47 with various proteins implicated in phenotypic modulation (alpha-smooth muscle actin, desmin, and vimentin) and fibrosis (type I, type III, and type IV collagens) was examined in young and old F 344 rat kidneys. Male F 344 rats often develop spontaneous nephropathy in old age. Kidneys obtained from 24-month-old F 344 rats showed glomerulosclerosis with marked tubulointerstitial damage including interstitial fibrosis, while no significant histological alteration was found in the kidneys of 6-month-old rats. Immunohistochemical analysis showed an increased accumulation of type I, type III, and type IV collagens in areas of glomerulosclerosis and interstitial fibrosis in old rat kidneys. In kidneys of young rats, collagen-binding HSP47 expression was weak in the glomeruli and occasionally seen in the interstitial cells. In contrast, strong immunostaining for HSP47 was noted in the glomeruli, tubular epithelial cells, and interstitial cells in kidneys of old rats. In addition, phenotypic alterations of mesangial cells and interstitial cells (immunopositive for alpha-smooth muscle actin), glomerular epithelial cells (immunopositive for desmin), and tubular epithelial cells (immunopositive for vimentin) were found in the kidneys of old F 344 rats. Double immunostaining showed that all these phenotypically altered renal cells express HSP47 and that increased expression of HSP47 was always associated with increased expression of collagens in the old rat kidneys. From the above observations, it is concluded that overexpression of HSP47 by phenotypically altered renal cells might play an important role in the excessive assembly of collagens and could thereby contribute to the glomerulosclerosis and interstitial fibrosis found in kidneys of aged F 344 rats.

Actins↗
PubMed1998

Monitoring of acute allograft rejection by cytological, immunocytochemical, and immunohistochemical studies following rat small-bowel transplantation.

We investigated the role of graft luminal fluid cytology for immunological monitoring of rat small-bowel allograft recipients. Allogeneic transplantation from WKAM (RT1u) to Lewis recipients and syngeneic transplantation using Lewis (RT11) rats were carried out. Twenty centimeters of the proximal jejunum was transplanted as a Thiry-Vella loop. The luminal fluid on days 0, 3, and 6 was examined cytologically using Papanicolaou, periodic acid-Schiff, and Giemsa staining, and immunocytochemically with monoclonal antibodies for macrophages (ED1 and ED2). Full thickness biopsies of graft tissue were evaluated by both immunofluorescence (ED1 and ED2) and by standard histological methods. The cytological examination on day 6 revealed an increase in the number of enterocytes, lymphocytes, and neutrophils, the presence of bacteria, and the depletion of goblet cells in the allografts. Histologically, significant morphological changes of acute rejection were first seen on day 6. Immunofluorescence predicted the acute rejection of the allografts earlier than a histological examination by showing an increase in the number of ED1- and Ed2-positive cells on day 3. Graft luminal fluid cytology and immunofluorescence analysis of ED1 and ED2 cells could thus be used to recognize early acute allograft rejection following small-bowel transplantation.

Animals↗
PubMed1998

Cortical motor neuron excitability during cutaneous silent period.

OBJECTIVE: To investigate cortical motor neuron excitability during cutaneous silent period (CSP), motor evoked potentials (MEPs) from abductor pollicis brevis following transcranial magnetic stimulation (TCM) were recorded with and without a conditioning of ipsilateral painful digital nerve electric stimulation. METHODS: MEPs following TCM were recorded with and without a conditioning stimulation at an interstimulus interval (ISI) from 0 ms to 100ms in 6 controls and four patients who had reduced pain sensation in unilateral upper limbs associated with cervical syringomyelia. In addition MEPs and evoked spinal cord potentials (ESCPs) from cervical epidural space following TCM with and without a conditioning stimulation were recorded in four patients with thoracic myelopathy. RESULTS: MEP amplitude was clearly attenuated by a conditioning stimulation at an ISI from 40 ms to 80 ms in controls (statistically significant at 60 ms). In patients with cervical syringomyelia, MEP amplitude was attenuated by a conditioning stimulation in asymptomatic hands similarly in controls but that was unchanged by a conditioning stimulation in the symptomatic hand with reduced pain sensation. In patients with thoracic myelopathy MEP amplitude was attenuated by conditioning stimulation similarly in controls, but ESCP amplitude was unchanged. CONCLUSIONS: We demonstrated that noxious cutaneous nerve stimulation suppressed spinal motor neurons but cortical motor neuron excitability was unchanged during CSP. In clinical practice, measurement of MEP suppression after noxious cutaneous nerve stimulation may provide useful information in patients with damaged pain related nerve fibers.

Adult↗
PubMed1998

Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) in advanced gastric cancer patients.

S-1 is a novel oral anticancer drug, composed of tegafur (FT), gimestat (CDHP) and otastat potassium (Oxo) in a molar ratio of 1:0.4:1, based on the biochemical modulation of 5-fluorouracil (5-FU). CDHP inhibits dihydropyrimidine dehydrogenase (DPD), an enzyme which degrades 5-FU, and maintains prolonged 5-FU concentrations in the blood and tumours. Oxo is distributed in the gastrointestinal tract at a high concentration after oral administration and alleviates gastrointestinal toxicity due to 5-FU. S-1 improves the tumour-selective toxicity of 5-FU by the actions of two modulators, CDHP and Oxo. We conducted a late phase II clinical trial of S-1 as an open trial in patients with advanced gastric cancer, to confirm its antitumour effect and adverse reactions. 51 patients with advanced gastric cancer were enrolled in the trial. S-1 was administered orally twice daily after meals, at a standard dose of 80 mg/m2/day. One course consisted of consecutive administration for 28 days and 14 days' rest. Administration was repeated over four courses. A complete response was obtained in 1 patient and partial responses in 24 patients, producing a response rate of 49% (25/51) (95% confidence interval (CI) 35.9-62.3%). The incidence of adverse reactions was 78% (40/51) and that of adverse reactions of grades 3 and 4 was 20%. Adverse reactions of grades 3 and 4 included a decrease in the haematocrit, leucopenia, granulocytopenia, diarrhoea, malaise and proteinuria. No serious unexpected adverse reactions were observed. In conclusion, S-1 was effective and well tolerated in patients with advanced gastric cancer.

Administration, Oral↗
PubMed1998

Longterm outcomes and quality of life after Z-shaped anastomosis for Hirschsprung's disease.

BACKGROUND: Z-shaped anastomosis is one of the modifications of Duhamel's procedure that was designed to eliminate the blind rectal pouch and to achieve complete resection of the colorectal septum. It has been the most widely performed operation in Japan for many years. The longterm postoperative function of evacuation and quality of life of the patients are considered important to evaluate this procedure. METHODS: At Kyushu University Hospital, from 1963 to 1997, 127 patients with Hirschsprung's disease underwent Z-shaped anastomosis. As a result, 122 out of 127 patients (96%) survived. The present status and symptoms, and anorectal functions, including a manometric study and barium enema, were evaluated during the clinical followup. RESULTS: A total of 99 of the 122 surviving patients (81%) were available for this study, and the mean postoperative period was 16 years. Evacuation scores in all patients were as follows; excellent, 62.2%; good, 28.6%; fair, 8.2%; and poor, 1.0%. The percentage of the patients who showed severe symptoms was 4.1% for diarrhea, 3.1% for constipation, 5.1% for incontinence, and 7.1% for soiling. The evacuation score improved chronologically and tended to reach a plateau at 10 to 15 years after operation, at which time 73% of the patients showed excellent outcomes and 95% were satisfactory (good or excellent). The appearance of a sense of defecation and an increase in the pressure difference between the anal canal and the rectum substantially contributed to the improvement in the defecation score. The appearance of the rectosphincteric reflex, including the atypical one, was seen in 40.5% of patients, but the appearance of a reflex did not seem to be related to the clinical status of defecation. Twenty-two of 30 patients older than 20 years were married, and 8 patients had children. CONCLUSIONS: The evacuation scores of in-patients undergoing Z-shaped anastomosis improved with age and were satisfactory (good or excellent) in most patients at least 10 years after operation. Most of the patients adapted to a normal social life.

Adolescent↗
PubMed1998

Neurite outgrowth-promoting factors in extracts of denervated chick skeletal muscle.

1. An extract of denervated skeletal muscle contained activity for promotion of neurite outgrowth from telencephalic neurons, as well as that from neurons in the spinal cord. A factor responsible for the activity was characterized in cultures of dissociated neurons. 2. The factor acted on neurons only when they were attached to the surface of culture dishes. Since treatments with proteases and lectins reduced the outgrowth-promoting activity, the factor was thought to be a glycoprotein. 3. Among the monoclonal antibodies raised against the partially purified extract, five antibodies were found to inhibit the activity for spinal and telencephalic neurons. The most potent antibody, 4D2a, recognized mainly a 63-kD protein and other minor proteins in the extract. Although the 63-kD protein was confirmed to be chick serum albumin by analysis of amino acid sequence, the purified albumin exhibited no activity. 4. From these observations, the factor was found to be a glycoprotein recognized by the neutralizing antibody as one of the minor components of the extract. This factor exhibits its activity in a substrate-bound form but not in a diffusible one.

Amino Acid Sequence↗
PubMed1998

Endothelin-1 binding to endothelin receptors in the rat anterior pituitary gland: interaction in the recognition of endothelin-1 between ETA and ETB receptors.

1. 125I-Endothelin (ET)-1 binding to the rat anterior pituitary gland was saturable and single, with a Kd of 71 pM and a Bmax of 120 fmol/mg. 2. When 1.0 microM BQ-123 (ETA antagonist) was added to the incubation buffer, the binding parameters were 8.3 pM and 8.0 fmol/mg, whereas 10 nM sarafotoxin S6c (ETB agonist) exerted little change in these binding parameters (Kd, 72 pM; Bmax, 110 fmol/mg). 3. ETB receptor-related compounds such as sarafotoxin S6c, ET-3, IRL1620, and BQ-788 competitively inhibited 125I-ET-1 binding, only when 1.0 microM BQ-123 was present in the incubation buffer. 4. Thus, the ETB receptor is capable of binding ET-1 when the ETA receptor is being occupied by BQ-123. A collaboration mechanism between the ETA and the ETB receptor may function in the recognition of ET-1, a typical "bivalent" ligand.

Animals↗