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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 541 records · Page 30Linked to original sources
PubMed1993

[Phase I clinical study of TT-62. Research group of TT-62].

TT-62 is a new derivative of FdUMP, which is the active metabolite of 5-FU. A phase I clinical study of TT-62 was conducted by a cooperative study. The same patients received single and 2-week oral administration of TT-62. Starting from 60 mg/m2 (1n), the dose was escalated to 420 mg/m2 (7n). In the single administration, the maximum tolerated dose (MTD) could not be determined. In the 2-week administration, MTD was 420 mg/m2, and the dose limiting factor was gastro-intestinal disturbances such as anorexia, nausea, vomiting and diarrhea. Increases in GOT.GPT and a decrease in hemoglobin content were observed. After administration was stopped all side effects disappeared. TT-62 was detected mainly in the plasma, while trace amounts of 5-FU and FUdR were also detected. TT-62 was excreted mostly in the urine, as alpha-fluoro-beta-alanine (FBAL). The cumulative urinary excretion of FBAL was about 80% of the total dose, and the oral absorption of TT-62 was thus thought to be good.

Administration, Oral↗
PubMed1993

Structure, expression and chromosomal mapping of c-akt: relationship to v-akt and its implications.

Sequence analysis of a nearly full-length murine c-akt cDNA clone and comparison with v-akt revealed the following: (a) The entire coding region of c-akt is identical to that of v-akt with the exception of five G to A transitions that do not alter the reading frame. The 3' untranslated regions of v-akt and c-akt are also identical with the exception of three single-base differences. (b) The recombination event that gave rise to v-akt occurred between the virus at nucleotide 785 from the Gag ATG codon and the 5' untranslated region of c-akt to 60 bp 5' from the c-akt ATG codon. (c) Three nucleotides absent from both Gag and c-akt were inserted at the junction between the two genes. The outcome of these events was to place, in frame, a 63-bp fragment between Gag and Akt. The resulting v-akt oncogene is predicted to encode a tripartite Gag (p12, p15, delta p30)-X-c-akt protein product. The c-akt protein contains, starting from its amino terminus, a src homology 2-like (SH2-like) domain, a domain rich in glutamic acid residues, part of which is predicted to form an amphipathic helix, and a kinase domain encoding a serine-threonine kinase with high degree of homology to members of the protein kinase C (PKC) family. The mouse c-akt is 90% homologous to human AKT1/RAC at the nucleic acid level and 98% homologous at the amino acid level. c-akt in the mouse is composed of 13 exons. The first exon contains a 5' untranslated GC-rich region. Since the recombination that gave rise to v-akt occurred with the 5' untranslated region, we hypothesize that the transduction of c-akt was preceded by provirus insertion upstream from or within the 5' untranslated region and in the same transcriptional orientation as the gene. c-akt was mapped by fluorescence in situ hybridization (FISH) to mouse chromosome 12 and rat chromosome 6 in close proximity to the Igh locus.

Amino Acid Sequence↗
PubMed1993

The proteins encoded by c-akt and v-akt differ in post-translational modification, subcellular localization and oncogenic potential.

The acute retrovirus AKT8, isolated from an AKR mouse T-cell lymphoma, transforms mink lung cells in culture and is oncogenic when inoculated into newborn mice. The oncogene carried by this virus, v-akt, arose by recombination between Gag and the 5' untranslated region of the cellular gene c-akt. v-akt encodes a 105 kilodalton (kd) Gag-Akt fusion protein which is phosphorylated on serine and threonine residues. c-akt encodes a 55 kd serine-threonine protein-kinase, which is related to members of the protein kinase C (PKC) family and contains an SH2-like domain. The SH2-like and catalytic domains of Akt were expressed in E. coli as fusions to the carboxy-terminus of the Maltose binding protein (MBP). Antibodies against these proteins were raised in rabbits and they were used to determine the potential myristylation and subcellular localization of the v-akt and c-akt protein products. Immunoprecipitation of v-akt and c-akt from lysates of [35S]methionine and [3H]myristic acid labeled AKT8 transformed mink lung cells revealed that only v-akt was myristylated. Fractionation of Dounce-homogenized cellular extracts from uninfected and v-akt-transformed mink lung and PA317 cells and from uninfected PC12 cells by differential centrifugation showed that while the c-akt protein was localized primarily in the cytosol (90%), the v-akt protein was dispersed among the cellular compartments with approximately 40% on the plasma membranes, approximately 30% in the nucleus and approximately 30% in the cytosol. To determine whether the differences in post-translational modification and subcellular distribution between c-akt and v-akt translated into oncogenicity differences between the two proteins, we used retrovirus based constructs to express them both in the nontumorigenic rat T cell lymphoma line 5675. Intraperitoneal (IP) inoculation of the parental and c-akt expressing 5675 cells in nude Balb/c mice revealed that neither was oncogenic. In sharp contrast to these results, v-akt expressing 5675 cells inoculated in nude Balb/c mice were found to be highly oncogenic.

Amino Acid Sequence↗
PubMed1992

[Athyreotic congenital hypothyroidism in two sisters].

Two sisters with athyreotic congenital hypothyroidism are described. This is the fifth report on athyreotic congenital hypothyroidism in siblings. The elder sister is 14 years old and the younger one is 12. The parents have no consanguinity or family history of thyroid disease. Both of the patients were born before the start of neonatal screening tests for congenital hypothyroidism. After birth, they had jaundice, abdominal distention and constipation, which are typical symptoms of congenital hypothyroidism. Serum T4 levels were decreased, and the serum TSH levels were markedly increased. Therefore we diagnosed them as having congenital hypothyroidism. They have received replacement therapy with thyroxine since diagnosis and have shown normal development physically and psychologically. They were tested for thyroid scintigram when the elder sister was 9 years old and the younger one was 7. 123I thyroid uptakes were 0.69% and 0.64%, respectively. The thyroid scans demonstrated no focus of accumulation of 123I. They do not have trapping defect of iodine, because 123I ratio of saliva and serum were 41.3 and 46.3, respectively. From these results, we diagnosed them as having athyreotic congenital hypothyroidism. They and their mother do not have any antithyroid antibodies. We suppose that some genetic factor is responsible for the athyreotic congenital hypothyroidism.

Child↗
PubMed1992

Immunological identification of a Cl- channel protein in electric organs of Narke japonica.

A Cl- channel in electric organs of Narke japonica was reconfirmed, using a polyclonal antibody, to be a 180k protein composed of two identical 90k units. The specific antibody against the 180k protein from electric organs reduced, when added in the cis side solution, the open probability of the Cl- channel in a planar bilayer membrane without affecting the single channel conductance, ion selectivity nor voltage dependency. Furthermore, the antibody added in the trans side also affected the channel to increase the open probability. The eluate of the immuno-affinity chromatography was found to contain only the 180k protein. These results indicate that 180k protein to be an integral membrane protein and to form the Cl- channel.

Animals↗
PubMed1992

Cytogenetic findings in a breast stromal sarcoma. Application of fluorescence in situ hybridization to characterize the breakpoint regions in an 11;19 translocation.

Cytogenetic analysis of a stromal breast sarcoma revealed a complex karyotype that included a reciprocal 11;19 translocation, along with multiple numerical changes, deletions, and other unbalanced structural rearrangements. Karyotypic abnormalities have not been reported previously in this rare neoplasm that arises from mesenchymal breast tissue, and the t(11;19) is of interest because various types of sarcoma are characterized by specific reciprocal translocations. Because of the pericentric nature of the breakpoints on chromosomes 11 and 19 in the t(11;19), classical cytogenetic banding could not reveal the centromeric origin of the translocation derivatives. Using nonisotopic in situ hybridization with chromosome 11 and 19 alpha-satellite probes, the centromere of each derivative chromosome was determined, and the rearrangement was interpreted as a balanced translocation, t(11;19)(q12 or q13.1;p12 or p13.1). This abnormality has not been described previously in any breast tumor.

Breast Neoplasms↗
PubMed1992

AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas.

We isolated cDNA clones containing the entire coding region of the putative oncogene AKT2. Sequence analysis and in vitro translation demonstrated that AKT2 encodes a 56-kDa protein with homology to serine/threonine kinases; moreover, this protein contains a Src homology 2-like domain. AKT2 was shown to be amplified and overexpressed in 2 of 8 ovarian carcinoma cell lines and 2 of 15 primary ovarian tumors. AKT2 was mapped to chromosome region 19q13.1-q13.2 by fluorescence in situ hybridization. In the two ovarian carcinoma cell lines exhibiting amplification of AKT2, the amplified sequences were localized within homogeneously staining regions. We conclude that AKT2 belongs to a distinct subfamily of protein-serine/threonine kinases containing Src homology 2-like domains and that alterations of AKT2 may contribute to the pathogenesis of ovarian carcinomas.

Amino Acid Sequence↗
PubMed1992

Inhibition of DNA polymerases by tripeptide derivative protease inhibitors.

Benzyloxycarbonyl(Z)-Leu-Leu-Leu-al and dansyl(Dns)-Leu-Leu-Leu-CH2Cl, well known as protease inhibitors, effectively inhibit the activities of DNA polymerases alpha, beta and gamma from rat liver and pol I from Escherichia coli, but the ability of these inhibitors to inhibit terminal deoxynucleotidyl transferase (TdT) is weak. The mode of inhibition by these tripeptide analogues is non-competitive with dNTP. The Ki values for Z-Leu-Leu-Leu-al and Dns-Leu-Leu-Leu-CH2Cl are 6.25 x 10(-5) M and 6.56 x 10(-5) M, respectively.

Amino Acid Sequence↗
PubMed1992

A muscle-derived factor antagonizes the neurotoxicity of glutamate in dissociated cell cultures of chick telencephalic neurons.

Excitatory amino acids including glutamate are known to reveal considerable neurotoxicity in various nervous systems. Our previous studies revealed that the chick muscle extract contains a factor which promotes the survival of telencephalic neurons. Further investigations clearly showed that this extract contains the factor that antagonizes the neurotoxicity of glutamate in a dissociated telencephalic neuronal culture system optimized for detection of the toxicity. This factor reduced at least the toxicity mediated by non-N-methyl-D-aspartate (non-NMDA) receptor.

Animals↗
PubMed1992

Immunoregulatory functions for murine intraepithelial lymphocytes: gamma/delta T cell receptor-positive (TCR+) T cells abrogate oral tolerance, while alpha/beta TCR+ T cells provide B cell help.

Past work has shown that a subset of effector T cells with unique characteristics could abrogate hapten- or antigen-induced tolerance, and the reconstitution of this immune response has been termed contrasuppression. We have studied contrasuppression in a model of oral tolerance (OT) in which adoptively transferred antigen-specific T contrasuppressor (Tcs) cells reverse OT and result in antibody responses to the eliciting antigen. In the present study, we show that murine intraepithelial lymphocytes (IELs) from mice orally immunized with sheep red blood cells (SRBC) contain T cells that exhibit Tcs cell activity. This effect was mediated by CD3+ gamma/delta T cell receptor-positive (TCR+), but not alpha/beta TCR+ T cells, and gamma/delta TCR+ Tcs cells were associated with both the CD4-,CD8+ and CD4-,CD8- (double-negative) IEL fractions. The CD4-,CD8+ gamma/delta TCR+ IELs were further separated into Vicia villosa-adherent and -nonadherent fractions. Adoptive transfer of V. villosa-adherent gamma/delta TCR+ T cells to mice with OT to SRBC resulted in splenic IgA, IgM, and IgG subclass anti-SRBC responses, while V. villosa-nonadherent gamma/delta TCR+ T cells were without activity. The gamma/delta TCR+ IELs did not support in vitro antibody responses in B cell cultures, while alpha/beta TCR+ IELs were effective T helper cells. Further, cytokine production by the gamma/delta TCR+ IELs was examined, and the gamma/delta TCR+ V. villosa-adherent fraction, which possessed contrasuppressor function, contained low levels of IL-5 mRNA and small numbers of IL-5-producing cells when compared with alpha/beta TCR+ IELs and V. villosa-nonadherent gamma/delta TCR+ IELs. Our results now show that mouse IELs contain two distinct types of T cells that function in the immune response, e.g., alpha/beta TCR+ T cells that produce IL-5 and function as helper cells, and gamma/delta TCR+ T cells that restore antibody responses in mice that had been orally tolerized with antigen.

Animals↗
PubMed1992

Capsaicin-sensitive nonadrenergic and noncholinergic depressor response to spinal cord stimulation in the pithed rat.

The effects of capsaicin on nonadrenergic, noncholinergic depressor responses to spinal cord stimulation were studied in pithed rats. Mean blood pressure (MBP was maintained at a level of 100 mmHg by continuous infusion of methoxamine and hexamethonium to block autonomic outflow. Electrical stimulation of the lower thoracic region (T9-12) via a pithing rod produced a frequency (1-8 Hz)-dependent fall in elevated MBP. The depressor response was abolished by tetrodotoxin, whereas atropine, propranolol, and cimetidine plus pyrilamine did not affect the response. Capsaicin treatment abolished the depressor response. These results suggest that spinal cord stimulation causes neurogenic vasodilation which is mediated by capsaicin-sensitive nonadrenergic and noncholinergic vasodilator nerves.

Animals↗
PubMed1992

Actin molecules promote neurite outgrowth of chick telencephalic neurons in vitro.

Chick brain extract contains protein factors for neurite outgrowth from embryonic chick telencephalic neurons in dissociated cell cultures. In the course of purification of the factors using a bioassay system, a 41 kDa protein was detected to be one of the factors. Immunoblot analysis showed that this protein is identical to actin. In addition, G-actin purified from rabbit skeletal muscle exhibits neurite outgrowth activity in the same dose-dependent manner as the 41 kDa protein. The same bioassay carried with other purified proteins did not show such a remarkable activity.

Actins↗
PubMed1992

Exercise testing and thallium-201 emission computed tomography in patients with intraventricular conduction disturbances.

The specificity of exercise thallium-201 emission computed tomography for coronary artery disease was assessed in patients with intraventricular conduction disturbances. Eighty-seven patients were studied: 33 with right bundle branch block (RBBB), 11 with RBBB and left-axis deviation, 11 with left (L)BBB, 12 on right ventricular pacing, and 20 with Wolff-Parkinson-White (WPW) syndrome. A control group of 349 consecutive patients with normal intraventricular conduction was also examined. The specificity of diagnosis of coronary artery disease in patients with LBBB (30%), right ventricular pacing (44%) or RBBB plus left-axis deviation (50%) was significantly lower than in patients with normal intraventricular conduction (94%; p less than 0.01). In contrast, there was no significant difference between specificity in patients with RBBB (86%) or WPW syndrome (90%) and patients with normal intraventricular conduction. Perfusion defects were found in the anterior, septal and inferior segments in patients with LBBB, and in the septal and inferior segments in patients with RBBB plus left-axis deviation despite the absence of coronary stenosis. Furthermore, diffuse slow washout was seen more often in patients with WPW syndrome (35%) than in controls who had normal intraventricular conduction (11%; p less than 0.05), despite a good exercise performance in the former group. This study suggests that there is an increased incidence of abnormal perfusion and clearance during exercise thallium-201 emission computed tomography in patients with intraventricular conduction disturbances.

Aged↗
PubMed1992

Intestinal intraepithelial lymphocyte T cells are resistant to lpr gene-induced T cell abnormalities.

The mucosal immune system of the gastrointestinal (GI) tract consists of Peyer's patches (PP), which are IgA inductive sites, and more diffuse effector regions which include cells in the intraepithelial lymphocyte (IEL) compartment. Since autoimmune MRL lpr/lpr (MRL/lpr) mice develop a proliferating CD3+, CD4-, CD8- (double negative; DN), B220+ T cell subset in systemic lymphoid tissue, we have initiated studies to determine the distribution of CD3+, DN, B220+ T cells (B220+ T cells or lpr/lpr T cells) in the GI immune system. Specifically, we examined T cell subsets separated according to expression of CD4, CD8, Thy-1, B220, alpha/beta T cell receptor (TcR) and gamma/delta TcR in PP and IEL of MRL/lpr mice at 6, 12 and 21 weeks of age. Increased numbers of CD3+ T cells were noted in both PP and spleen of 12- and 21-week-old mice in which the development of autoimmune disorders were also evident. However, normal numbers of CD3+ IEL T cells were seen in MRL/lpr mice in all three age groups tested. When the presence of T cell lymphadenopathy was examined in both IgA inductive and effector tissues, the PP followed the B220+ T cell pattern seen in the spleen, where approximately 30%-50% of CD3+ T cells in the PP of 12- and 21-week-old MRL/lpr mice expressed the phenotype of lpr/lpr T cells and greater than 90% were alpha/beta TcR+. On the other hand, B220+ T cells had not developed in PP or spleen of 6-week-old MRL/lpr mice. Of interest was the finding that IEL from lpr/lpr homozygous mice did not contain B220+ T cells in any age group tested. In this regard, the IEL of MRL/lpr mice comprised an identical pattern and frequency of CD4-/CD8+, CD4+/CD8-, DN and CD4+/CD8+ (double positive, DP) T cell subsets as their normal counterparts (i.e. MRL +/+, BALB/c and C3H/HeN mice) which consisted of approximately 75%, approximately 7.5%, approximately 7.5% and approximately 10%, respectively. Further, Thy-1, gamma/delta TcR and alpha/beta TcR expression in these four subsets of MRL/lpr IEL were very similar to normal mice. These results suggest that the intestinal IEL compartment is minimally affected by the lpr/lpr mutation which induces T cell abnormalities and indicate that B220+ T cells do not preferentially home to IEL. Further, our results support the concept that IEL T cells develop as a separate T cell lineage from thymus-derived cells.

Animals↗
PubMed1992

K+ channel involvement in induction of synaptic enhancement by mast cell degranulating (MCD) peptide.

A bee venom, mast cell degranulating peptide (MCD), which induces long-term potentiation (LTP) of synaptic transmission in hippocampal slices, was found to possess multiple functions. They include (1) binding and thereby inhibiting a voltage-dependent K(+)-channel in brain membranes, (2) incorporation in a lipid bilayer to form voltage-dependent and cation-selective channels by itself, and (3) activation of a pertussis toxin (Ptx)-sensitive GTP-binding proteins. In this study, we prepared several derivatives and analogues of MCD and investigated which function is more closely related to the induction of LTP. Another bee venom, apamin, formed ion channels in a lipid bilayer which were indistinguishable from those formed by MCD. D-MCD, an optical isomer of MCD, activated a Ptx-sensitive GTP-binding protein. However, these peptides did not induce LTP in the hippocampal slices. A snake venom, dendrotoxin-I (DTX-I), bound to the same K(+)-channels as MCD and did induce LTP. These results suggest that the most potent aspect of MCD involved in LTP inducibility is its interaction with the voltage-dependent K(+)-channel.

Animals↗
PubMed1992

Manometric evaluation of gastrointestinal motility in a case of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS).

We report on a manometric study of the esophagus, stomach, duodenum, jejunum and anorectum in a case of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS). An esophageal examination showed normal esophageal contractions and a positive rectoanal reflex was obtained in an anorectal manometry. However, the continuous fasting manometric recording of the antrum, duodenum and jejunum lasting a total of 12 hours revealed a severe motility disturbance of the gastrointestinal tract. During the examination a band of low amplitude contractions was observed in the antrum only once and it was followed by small rhythmic contractions of the duodenum, but none of propagated or spontaneous contractions were seen in the jejunum.

Child, Preschool↗
PubMed1992

Malignant lymphoma of the breast. Immunologic type and association with lymphocytic mastopathy.

Clinical and pathologic findings in 19 cases of primary non-Hodgkin's lymphoma of the breast collected from several hospitals in Japan were reviewed. All patients were women (median age, 45 years) and they usually had breast masses that had recently become enlarged. The sites of the lesions were the right breast in eight cases, the left breast in eight, and both breasts in one. The locations of two masses were unknown. Lymphoma recurred in the opposite breast in three cases 14, 23, and 23 months after surgery. Histologically, diffuse large cell lymphoma was the most common form of disease (63%). One lesion was a follicular lymphoma. The so-called lymphoepithelial lesion, a characteristic finding for mucosa-associated lymphoid tissue type lymphomas, was observed in eight cases (42%). Immunohistochemical analysis revealed that all but two tumors were of B-cell type; such findings confirmed morphologically based conclusions. Histologic and immunohistochemical evidence of lymphocytic mastopathy, a recently described autoimmune disease of the breast, was found in most of the cases. Formation of lymphoid follicles in or around the tumors was found in five cases (26%). Based on these findings, it is suggested that most mammary lymphomas are B-cell tumors and they may be associated with coexisting or antecedent lymphocytic mastopathy.

Adult↗