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Biomedical subjects

M Noguchi

Publications and source records attributed to M Noguchi.

At least 307 records · Page 17Linked to original sources

[Effect of ritodrine hydrochloride on fetal perfusion pressure in dually perfused human placenta].

Ritodrine hydrochloride is widely used in clinical obstetrics for the prevention of premature labor, but the knowledge of its effect on fetal circulation is limited. The purpose of this study was to elucidate changes in vascular resistance in the fetal placental circulation by using the dually perfused human placenta in vitro. The viability of the perfused placenta was maintained during the experiments because the production rate of hCG was constant. The transfer of ritodrine hydrochloride was observed and its concentration on the fetal side was about one third of maternal side at 120 min subsequent to the injection. The fetal perfusion pressure during the control period was 38.6 +/- 7.0 mmHg (mean +/- S.D., n=3). After the addition of ritodrine hydrochloride to the maternal circulation, the fetal perfusion pressure was decreased dose-dependently. The pressure was 95.4 +/- 1.8% at 80 ng/ml of ritodrine hydrochloride which was within the clinical concentration limits. It is concluded that ritodrine hydrochloride acts as a vasodilator on the fetal vasculature in the human placenta.

Adrenergic beta-Agonists↗

Enhanced interferon-gamma production and B7-2 expression in isolated intestinal mononuclear cells from patients with Crohn's disease.

Many of the in vivo activities of interferon (IFN)-gamma match the changes found in inflammatory bowel disease, but its importance is controversial. Interferon (IFN)-gamma induces the expression of B7-2 costimulatory molecules on monocytes. We measured levels of IFN-gamma production in intestinal mucosa and isolated lamina propria mononuclear cells (LPMC) in patients with Crohn's disease (CD) and ulcerative colitis (UC). We also investigated the induction of B7-2 on the LPMC by flow cytometry. Mucosal IFN-gamma production was higher than the control level in patients with CD, but this was not the case in UC. IFN-gamma production and B7-2 expression in the LPMC of CD were higher than in the LPMC of UC and controls, and high levels of B7-2 expression were observed on the LPMC of CD after incubation with endotoxin. The induction of B7-2 on the LPMC of CD may provide a mechanism for the amplification of T cell proliferation and lymphokine production by IFN-gamma-activated LPMC.

Adult↗

[Usefulness of the 24-hour delayed film of upper gastrointestinal series for the diagnosis of sigmoidovesical fistula: report of 3 cases].

Recently, sigmoidovesical fistula is not a rare disease as a result of the change of our food style and increase in the age ratio. However, in general, the preoperative image diagnosis is difficult. We have experienced three cases of sigmoidovesical fistula, examined by barium enema, cystography, upper gastrointestinal series, cystoscopy, colonic fiberscopy and computed tomography. The fistulas were identified preoperatively by the 24-hour delayed film of upper gastrointestinal series. By this method, the regions of sigmoidovesical fistula were identified, and the patients were operated. We concluded that the 24-hour delayed film in upper gastrointestinal series might be useful to diagnose the sigmoidovesical fistula.

Adult↗

Controversies in the Surgical Management of Operable Breast Cancer.

The literature is reviewed regarding the surgical management of breast carcinoma, and controversies are discussed. Several unresolved issues remain in the surgical management of breast carcinoma. First, the optimal surgical treatment of patients who are at increased risk for having internal mammary lymph node metastases remains unknown. Second, it remains controversial whether axillary dissection is therapeutic or merely represents a staging procedure. Third, there is no consensus regarding the optimal extent of resection prior to irradiation in breast-conserving treatment. Nevertheless, breast conservation is generally accepted as a preferable therapy in patients with operable breast carcinoma, while modified radical mastectomy, with or without breast reconstruction offers an acceptable alternative for these patients.

Journal Article↗

A Case with Breast Cancer under the Nipple Who Underwent Breast Conserving Treatment.

Although breast conserving treatment (BCT) had become the standard therapy for early breast cancer, breast removal is still recommended for patients with a tumor beneath the nipple or with Paget's disease. We have employed transposition of a latissimus dorsi myocutaneous (LD-MC)flap after wide local excision of a tumor with the nipple-areola complex. A new nipple-areola complex was reconstructed on the LD-MC flap after breast irradiation. Utilizing reconstructive techniques, BCT will likely become the treatment of choice for more patients with early breast cancer.

Journal Article↗

Human 5-lipoxygenase associates with phosphatidylcholine liposomes and modulates LTA4 synthetase activity.

A Ca2+ and a phosphatidylcholine (PC) as stimulatory factors to human 5-lipoxygenase (5-LO) were assessed to examine aspects of the regulatory mechanism of 5-LO. In the presence of Ca2+ (1 microM or less), PC liposomes distinctly stimulated the dual activities of 5-LO for the production of 5-HPETE from arachidonate and for its subsequent conversion to LTA4. At the same concentration of Ca2+, 5-LO was found to bind to PC liposomes. As with 5-LO activities, the binding was dependent on the range of Ca2+ concentration. The conversion ratios of 5-HPETE to LTA4 were dependent on PC liposome concentration and reached a maximum of 50% conversion. Among the four cell membrane lipids examined, PC liposomes demonstrated the highest conversion ratio of 5-HPETE to LTA4 by 5-LO. Most of the arachidonate added to the reaction mixture localized in PC liposomes. These results confirm that the intracellular increase of Ca2+ concentration causes 5-LO to associate with the cell membrane and perform an interfacial reaction. They also suggest that this binding of 5-LO to the cell membrane enhances the subsequent conversion from 5-HPETE to LTA4.

Adenosine Triphosphate↗

Characterization of an antisense Inr element in the eIF-2 alpha gene.

We recently discovered an opposing initiator promoter (Inr) downstream of the sense promoter region of the eIF-2 alpha gene (Silverman, T., Noguchi, M., and Safer, B. (1992) J. Biol. Chem. 267, 9738-9742). By reverse transcriptase/polymerase chain reaction analysis of G0 and activated (G1) T-lymphocyte RNAs, overlapping sense and antisense transcripts are now identified. Sense transcription of the eIF-2 alpha gene proceeds from left to right to generate alpha-mRNA; antisense transcription proceeds from right to left to generate RNA, having a sequence complementary to eIF-2 alpha mRNA. Upstream indicates a position 5' relative to the transcription start site. Using DNase I footprint analysis and EMSA, we have found a potential cis-regulatory sequence immediately upstream of the Inr which binds a 43-kDa protein. In addition to conferring protection against DNase I (+457 to +474), the factor also generates hypersensitive sites directly over the Inr (+447 to +457). Insertion of the Inr footprint region into a luciferase reporter gene construct increases expression 150-fold. While mutation of the Inr conserved sequence decreases luciferase activity by 50%, mutation of the 43-kDa factor binding site inhibits luciferase activity by 20%. Sense orientation of the Inr footprint region decreases activity by 80%. The 43-kDa Inr-associated binding protein may be involved in allowing access of RNA polymerase II transcription complexes ot the initiation site of this TATA-less gene. A model for the regulation of eIF-2 alpha expression involving the rapid degradation of dsRNA generated by the relative activities of the two overlapping and opposing promoters is proposed.

Base Sequence↗

Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID.

Interleukin-2 (IL-2) signaling requires the dimerization of the IL-2 receptor beta.(IL-2R beta) and common gamma (gamma c) chains. Mutations of gamma c can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain gamma c), and IL-9 (whose receptor is shown here to contain gamma c) induced the tyrosine phosphorylation and activation of the Janus family tyrosine kinases Jak1 and Jak3. Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively; IL-2 induced Jak3-IL-2R beta and increased Jak3-gamma c associations. Truncations of gamma c, and a gamma c, point mutation causing moderate X-linked combined immunodeficiency (XCID), decreased gamma c-Jak3 association. Thus, gamma c mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCID-like phenotype.

Animals↗

Immunohistochemical Detection of p53 and c-erbB-2 Proteins: Prognostic Significance in Operable Breast Cancer.

We examined the associations of p53 expression and/or c-erbB-2 expression with Ag-NOR counts and clinicopathologic variables in 111 breast cancer patients, and assessed whether expression of either p53or c-erbB-2 would be useful prognostic indicators. There was no significant association between p53 expression and c-erbB-2 expression, but p53 expression and c-erbB-2 expression, especially in combination, were shown to be significantly associated with Ag-NOR counts and axillary lymph node metastasis. Although p53 expression and c-erbB-2 expression were significant prognostic factors by univariate analysis, they did not appear to be independent prognostic factors by multivariate analysis, in which nodal status was introduced using the Cox model. When nodal status was excluded from the model, however, concurrent p53 and c-erbB-2 expression did have a significant prognostic value. Therefore, it was suggested that concurrent p53 and c-erbB-2 expression provides valuable prognostic information for breast cancer patients in whom axillary lymph node dissection has not been performed.

Journal Article↗

Interfacial kinetic reaction of human 5-lipoxygenase.

The kinetics of human 5-lipoxygenase were investigated in the presence of Tween 20 using a continuous spectrophotometric assay. Using the mixture at a constant molar ratio of arachidonate/Tween 20 at pH 8.0, the steady-state velocity on a varied arachidonate concentration did not follow simple Michaelis-Menten-type kinetics and double-reciprocal plot analysis gave hyperbolic curves. However, by introducing the concept of a local pH change, it was possible to analyze the kinetics as simple Michaelis-Menten type. The concept of a local pH change implies that when utilizing an acidic and amphiphilic substance as a substrate, such as arachidonate, the medium around the substrate is acidified with an increased concentration of substrate. This concept was explained rationally by two experiments. Consequently, the data were transformed according to a local pH change and analyzed according to a dual phospholipid model as has been proposed for phospholipase A2 [Hendrickson, H. S. and Dennis, E. A. (1984) Kinetic analysis of the dual phospholipid model for phosphalipase A2, J. Biol. Chem. 259, 5734-5739]. It is concluded that 5-lipoxygenase performs an interfacial reaction in the arachidonate/Tween 20 mixed micelles in the same manner as phospholipase A2. The values of Km were almost constant (about 0.07 molar fraction), even when arachidonate molar ratios were changed in the surface of the mixed micelles. The values for Ks (the association constant of the enzyme to the micelle interface) ranged over 0.21-0.48 microM. The Vmax was 25.76 mumol.min-1.mg-1. This concept of a local pH change could be used extensively with enzymes which utilize both amphiphilic and acidic substances as substrates.

Arachidonate 5-Lipoxygenase↗

[Case report of sister with Duane's syndrome and PGA, or myasthenia gravis].

We report a case of polyglandular autoimmune syndrome (PGA) complicated by Duane's syndrome. The patient was 44-year-old female with marked limitation of abduction in the left eye, lethargy, nonhomogeneous facial pigmentation, goiter, and oligomenorrhea. A diagnosis of chronic thyroiditis was first made to explain the patient's symptoms. Laboratory examinations were performed. Plasma ACTH level was high and plasma cortisol was low, and there was no response to the ACTH stimulation test. The presence of primary adrenocortical deficiency was confirmed. Moreover, primary gonadal failure was also present, and the diagnosis of PGA type II was made. The patient's elder sister had myasthenia gravis which is a condition known to occur with PGA type II. Therefore, the sister was also suspected to have PGA type II, as the syndrome can occur in family members. However, since she had been receiving large doses of steroids for her myasthenia gravis, laboratory findings were inconclusive. Duane's syndrome, which is characterized by congenital oculomotor disturbance, was also seen in the sister. It is still unknown whether the familial occurrence of Duane's syndrome has a genetic basis. There have been reports of congenital disorders occurring in combination with autoimmune diseases. Further investigation into the relationship between congenital anomalies and autoimmune diseases is necessary.

Adult↗

Nuclear immunoreaction of p53 protein in soft tissue sarcomas. A possible prognostic factor.

BACKGROUND: Tumor suppressor gene p53, located on the short arm of chromosome 17, frequently mutates in various types of cancers and plays a critical role in the multiple stages of carcinogenesis. However, there is little information about the clinicopathologic significance of alterations of the p53 gene in soft tissue sarcomas (STS). METHODS: Because it is known that nuclear accumulation of p53 protein correlates closely with the presence of mutations in the p53 gene, immunohistochemical detection of this protein was performed. A polyclonal antibody (RSP-53) raised against synthetic human p53 peptide was used to detect nuclear accumulation of the protein. Pathologic specimens of 96 patients with STS were collected from the surgical pathology files of the National Cancer Center Hospital and examined. RESULTS: Nuclear accumulation of p53 protein was detected in 31 (32.3%) patients. The percentage of patients with a positive immunoreaction was high in patients with malignant schwannoma (100%), rhabdomyosarcoma (71.4%), and synovial sarcoma (50.0%), whereas it was low in patients with liposarcoma (13.6%) and 0% in those with fibrosarcoma. It was closely associated with the histologic grade of malignancy (grade 1, 12.0%; grade 2, 30.8%; grade 3, 44.4%) and the patient's age (younger than 40 years, 46.9%; 40 years of age or older, 25.0%). Both overall and metastasis-free survival rates were significantly lower for patients with a nuclear p53 immunoreaction than for those without it. CONCLUSIONS: The nuclear p53 immunoreaction is considered a marker of tumor aggressiveness and appears to be a useful prognostic factor for STS.

Adolescent↗

Healing of the rabbit medial collateral ligament following an O'Donoghue triad injury: effects of anterior cruciate ligament reconstruction.

The effects of healing time and anterior cruciate ligament reconstruction on healing of the medial collateral ligament and stability of the knee joint were evaluated in a rabbit model of an O'Donoghue triad injury (rupture of the medial collateral ligament with removal of the anterior cruciate ligament and part of the medial meniscus). At time 0 and at 6 and 12 weeks postoperatively, the anterior-posterior translation and varus-valgus rotation of the knee, the structural properties of the femur-medial collateral ligament-tibia complex, and the mechanical properties of the substance of the medial collateral ligament were evaluated. Although anterior-posterior translation increased significantly with time, we could not demonstrate a significant temporal effect on varus-valgus rotation. The ultimate load, elongation at failure, and energy absorbed to failure improved with time. In addition, with time, failure of the complex occurred more often in the ligament substance than at the osseous insertion. Because healing time did not affect the cross-sectional area or modulus of the medial collateral ligament, the improved structural properties of the complex resulted not from improvements in the mechanical properties of the tissue but rather from healing of the tibial insertion site. By 12 weeks, the reconstructed knees had only minor signs of osteoarthrosis on the tibiofemoral surfaces; this is in contrast to the findings in anterior cruciate ligament-deficient knees in our earlier study. Additionally, at 12 weeks, the stiffness of the complexes from the reconstructed group was 1.3 times that of the anterior cruciate ligament-deficient group (p < 0.05), and te ultimate load had increased by a factor of 1.6 (p < 0.05). Our findings demonstrate that reconstruction of the anterior cruciate ligament in the rabbit helps to stabilize the joint, improves healing of the medial collateral ligament, and may decrease the incidence of early-onset osteoarthrosis after an O'Donoghue triad injury.

Animals↗

Unique T cell differentiation markers: gangliosides with cholera toxin receptor activity on murine fetal thymocytes.

Cholera toxin B subunit receptors (CTBR; gangliosides GM1a and GM1b-GalNAc-Gal) and GM1b-type gangliosides were examined during T cell development in BALB/c mice by FACS or TLC immunostaining. Sixty-two percent of CD4-8- early fetal thymocytes express CTBR [58% low affinity (GM1a+), 4% high affinity (GM1a2+)] at 13 days gestation (Day 13); GM1a2+ was expressed preferentially on Thy-1+ fetal thymocytes after Day 13. GM1a2+ Thy-1+ cells increased from 4% on Day 13 to 95% on Day 17. Surface GM1a2+ decreased beginning on Day 15 while GM1b-GalNAc-Gal (and CD4 and CD8) increased. GM1b-type+ cells increased from 8% on Day 13 to 51% on Day 17 and then decreased to 16% at 4 weeks; few asialo GM1+ cells (< 5%) are seen during gestation. Thus, synthesis of GM1a- and GM1b-type series was active until Days 15 and 17, respectively, and then was suppressed; GM1b-GalNAc-Gal was synthesized from GM1b following Gestational Day 15. GM1a- and GM1b-type identify immature T cells in mice, while GM1b-GalNAc-Gal identifies mature T cells.

Animals↗

The ter primordial germ cell deficiency mutation maps near Grl-1 on mouse chromosome 18.

A single recessive gene, ter (teratoma), causes germ cell deficiency and a high incidence of congenital testicular teratomas in the 129/Sv-ter strain of the mouse. Linkage analyses between the ter gene and 36 marker genes of 19 chromosomes were performed with matings between the C57BL/6J-ter congenic strain and four inbred strains. Results showed that the ter gene was linked to D18Mit9, D18Mit14, and D18Mit17 on Chromosome (Chr) 18. Gene order estimated on the basis of recombination distance (in centimorgans) was [centromere-D18Mit14-5.1 (cM)-ter-0 (cM)-D18Mit17-23.8 (cM)-D18Mit9]. D18Mit17 is the microsatellite DNA of the Grl-1 (glucocorticoid receptor-1) locus. We conclude that the ter gene is closely linked to Grl-1 on Chr 18 and is a new mutation involving the developmental modification of primordial germ cells in mice.

Animals↗

Studies of effects of anticancer agents in combination with/without hyperthermia on metastasized human bladder cancer cells in chick embryos using the polymerase chain reaction technique.

Cultivated T24 cells derived from a human bladder cancer were inoculated into the chorioallantoic membrane vein of chick embryos. Hyperthermic treatment was performed following injection of anticancer agents 3 days after the inoculation of the T24 cells. DNA samples were obtained from the livers of the chick embryos, and the polymerase chain reaction technique was used to amplify a DNA fragment specific to the human beta-globin gene. The Southern hybridization method was used to evaluate the inhibitory effects of anticancer agents in combination with/without hyperthermia on T24 cells metastasized to the liver. The hyperthermia exerted an inhibitory effect on the growth of the T24 cells in the livers of the chick embryos, and this was dependent on the thermal dose. The antitumor effects of hyperthermia performed at 42.5 degrees C for 20 min and at 43.0 degrees C for 10 min were evidenced by 69.2% an 82.0% inhibition of the growth of the metastasized T24 cells, respectively, as compared with the growth of untreated T24 cell. Hyperthermia performed at 42.5 degrees C for 10 min alone produced 26.7% tumor growth inhibition, and these conditions for hyperthermia were subsequently used as a criterion for evaluating the effects of its combination with various anticancer agents. Adriamycin (20 micrograms/egg) alone, mitomycin C (10 micrograms/egg) alone, carboplatin (10 micrograms/egg) alone, and cisplatin (10 micrograms/egg) alone produced 13.5%, 58.9%, 27.3%, and 29.1% tumor growth inhibition, respectively. Adriamycin and mitomycin C applied in combination with hyperthermia showed additive inhibitory effects on the growth of the metastasized T24 cells in this chick embryo model.

Animals↗