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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 19 recordsLinked to original sources

[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

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

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

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

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

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

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

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

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

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

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

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

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

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

Augmentation of beta adrenergic receptors in cardiomyopathic hamsters (BIO 14.6) with heart failure.

OBJECTIVE: The aim was to characterise the transmural distribution of beta adrenergic receptors in failing myocardium in cardiomyopathy. METHODS: Using a quantitative autoradiographic technique with 125I-cyanopindolol (ICYP), the density and transmural distribution of beta adrenergic receptors were compared between eight cardiomyopathic BIO 14.6 Syrian hamsters with heart failure and six normal age matched controls (BIO 14.6HAM). RESULTS: Binding of ICYP to transmural slices of hamster myocardium was rapid, saturable, stereoselective, and displaceable by antagonists. The binding isotherm showed a significant increase in the total tissue content of beta adrenergic receptors in the failing myocardium of cardiomyopathic hamsters: 15.3(SEM 1.6) fmol.mg-1 protein v 9.4(1.2) fmol.mg-1 protein in normal myocardium of control hamsters (p < 0.05). There was no difference in receptor affinity. Quantitative autoradiography showed regional heterogeneity of beta adrenergic receptors in cardiomyopathic hamsters, with an increase of beta adrenergic receptor density in the septal and subendocardial regions. In addition, the regions with increased interstitial fibrosis corresponded to the sites of increased beta adrenergic receptor density. CONCLUSIONS: The transmural distribution of beta adrenergic receptor is heterogeneous in the failing myocardium of cardiomyopathic hamsters and an increased beta adrenergic receptor density may be associated with the development of cardiomyopathy.

Animals

Selective induction of Th2 cells in murine Peyer's patches by oral immunization.

We have used three different methods to determine the T helper (Th) cell response, including Th1 and Th2 types, in murine Peyer's patches (PP) following oral immunization with sheep red blood cells (SRBC). These include: (i) use of cytokine-specific (IFN-gamma and IL-5), single cell assays to estimate the frequencies of Th1 and Th2 cells respectively, (ii) cytokine-specific mRNA--cDNA dot blot and Northern gel hybridizations to detect levels of specific mRNA, and (iii) T cell cloning techniques to determine the frequency of Th1 and Th2 clones. Mice were immunized with SRBC by either the oral or i.p. route. The PP and splenic (SP) CD3+ and CD3+ CD4+ T cell subsets were isolated and cultured with antigen, feeder cells, and IL-2, and were assessed at various intervals (days 0, 1, 3, and 6) for numbers of T cells producing either IFN-gamma or IL-5 by use of an enzyme-linked immunospot (ELISPOT) procedure. Cultures of T cells from PP or SP of mice given SRBC by the oral route had a high frequency of IL-5 spot forming cells (SFC), with lower numbers of IFN-gamma SFC. However, cultures of CD3+ T cells and CD3+ CD4+ Th cells from spleens of i.p. immunized mice exhibited predominantly IFN-gamma SFC, with smaller but significant numbers of IL-5 SFC. This distinct pattern of cytokine production was supported by mRNA analysis where high IL-5 specific mRNA levels were noted in PP T cell cultures of orally primed mice, while IFN-gamma mRNA was predominant in the SP CD3+ T cell and CD3+ CD4+ Th cell cultures from i.p. immunized mice. When the frequencies of IFN-gamma or IL-5 SFC were assessed among cloned Th cells from orally- or systemically-immunized mice, 74% of Th cell clones from PP of mice orally immunized with SRBC were IL-5 producers (Th2 type), while 67% of Th cell clones from SP of mice immunized by the i.p. route were IFN-gamma producers (Th1 type). Our studies show that higher frequencies of IFN-gamma producing Th1-type cells occur in SP of mice given antigen by the systemic route, while oral immunization results in predominantly IL-5 producing, Th2-type cells in PP.

Administration, Oral

Evaluation of UW solution for preservation of small intestinal transplants in the rat.

Simple cold preservation was evaluated in the rat model of small intestinal transplantation. Lewis rats received a syngeneic heterotopic graft of the jejunum either immediately (SI) or after preservation for 24 hr in Euro-Collins (SPE24), for 48 hr in EC (SPE48), for 24 hr in University Wisconsin solution (SPW24), or for 48 hr in UW (SPW48). The survival rates of SI, SPE24, SPE48, SPW24, and SPW48 were 100%, 78%, 0%, 100%, and 33%, respectively. Physiologic and pharmacologic properties of the grafts and native intestine were evaluated in vitro between 8 and 12 days after transplantation. Smooth muscle in all specimens contracted in response to cholinergic agonists, phenylephrine, and substance P, and was relaxed by isoproterenol. Excitatory innervation was present in 100%, 100%, 100%, and 67% of SI, SPE24, SPW24, and SPW48, respectively, while inhibitory innervation in each group was 50%, 29%, 60%, and 0%. Thus, smooth muscle function was preserved in all groups, but neural activity was impaired by some of the storage conditions. Preservation was best in SPW24, which had physiologic responses similar to those of SI. The rat jejunum can, therefore, be preserved in good condition for up to 24 hr before transplantation using simple cold storage in UW solution.

Acetylcholine

The effect of breast self-examination on early detection and survival.

To investigate the effect of breast self-examination (BSE), we compared the stages, survival, and the risk of death for 355 patients with breast cancer detected by BSE with those for 1,327 patients with breast cancer detected by chance. The early stages of the disease were found to be more common among the symptomatic breast cancer patients detected by BSE than those by chance. The 5-year overall survival rate was 94.4% for the symptomatic patients detected by BSE, and was significantly higher by 8.7% than that (85.7%) for patients detected by chance (P less than 0.001). The 10-year survival rate was 81.6% for patients detected by BSE, and 76.6% for cases detected by chance (the difference was not significant). The overall difference between the two survival curves was statistically significant by the logrank test (P less than 0.01). A multivariate analysis using the Cox proportional hazards model showed that the risk of death for patients detected by BSE was smaller by 0.570 times than that for patients detected by chance, which was statistically significant (P less than 0.05). The effect of biases inherent to BSE in the survival analysis cannot be controlled completely even after conducting multivariate analysis. These results suggest that BSE may contribute to the reduction of the risk of death through early detection of breast cancer. However, further examination should be conducted by other methods to obtain conclusive evidence.

Breast Neoplasms