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Biomedical subjects

R Inoue

Publications and source records attributed to R Inoue.

At least 145 records · Page 8Linked to original sources
PubMed1994

Bilateral Breast Cancer in a Patient with a Strong Family History of Cancer: Analysis of p53 Germ Line Mutations.

We report a case of bilateral breast carcinoma in a patient with a strong family history, including 4 cases of breast carcinoma, 1 case of prostate carcinoma (father), 1 case of hepatocellular carcinoma (mother), 2 cases of gastric carcinoma, 1 case of lung carcinoma, and 1 case of lingual carcinoma, in second degree relatives, together with analysis of germ line p53 mutations. The patient was a 51-year-old female who had undergone mastectomy 9 years previously for an invasive ductal carcinoma of the right breast. Lymph nodes were free of metastases and the tumor had negative estrogen receptor (ER) status. Bone and lung metastases developed 18 months after surgery, and had been well controlled with chemoendocrine therapy. She subsequently underwent a modified radical mastectomy for carcinoma in the contralateral breast. This was an invasive lobular carcinoma with negative lymph node metastasis, negative p53 immunoreaction, negative c-erbB-2 protein and positive ER status. In this breast-prostate carcinoma-type cancer family there was a high incidence of breast carcinoma; the father, who had prostate carcinoma, was possibly a carrier of a breast carcinoma susceptible gene. We have however detected to p53 germ line mutations in the lymphocytes DNA of the patient and her niece. The accumulation of cancers in this family line remains to be elucidated further using other genetic markers.

Journal Article↗
PubMed1994

A possible role of tyrosine kinases in the regulation of muscarinic receptor-activated cation channels in guinea pig ileum.

We investigated the effects of inhibitors for tyrosine kinases and phosphatases on the muscarinic receptor-activated nonselective cationic current. With nystatin-perforated whole-cell recording, the tyrosine kinase inhibitor genistein (1 approximately 10 micrograms/ml) reduced the amplitude of currents evoked by iontophoretically applied acetylcholine in a dose-dependent manner, the maximum inhibition being to about 46% of the control. In contrast, daidzein (10 micrograms/ml), an inactive analog of genistein, exerted little effect. These effects were unchanged when the cationic current was activated by internal perfusion of GTP gamma S (50 microM) bypassing the muscarinic receptor. A potent phosphatase inhibitor, orthovanadate (30 approximately 100 microM), on the other hand, increased the GTP gamma S-induced cationic current. These results suggest that tyrosine phosphorylation may be essential to regulate the Ca mobilization associated with muscarinic receptor-operated nonselective cation channels.

Acetylcholine↗
PubMed1994

Preferential inhibition of inducible nitric oxide synthase by ebselen.

Ebselen, 2-phenyl-1,2-benzisoselenazole-3(2H)-one can preferentially inhibit the activity of inducible nitric oxide (NO) synthase with little inhibition of endothelial constitutive NO synthase within a certain concentration range. This suggests that ebselen deserves further in vivo studies to examine its possible application to the therapy of septic shock where inducible NO synthase is responsible for vasodilation.

Amino Acid Oxidoreductases↗
PubMed1994

Structure and function of nitric oxide synthases.

Nitric oxide (NO), which accounts for the biological activity of endothelium-derived relaxing factor, is now thought to play a variety of roles in the nervous system and in immunologic reactions. NO is synthesized from L-arginine by nitric oxide synthase (NOS). There are three isoforms of NOS; type I (neuronal), type II (inducible), and type III (endothelial). The fundamental structure of the three isoforms, which contain calmodulin-, FMN-, FAD-, and NADPH-binding domains, is the same. Calmodulin is already bound to inducible NOS without requiring Ca2+, while the others are Ca2+/calmodulin-dependent. Endothelial NOS is bound to membranes by N-myristoylation, while the other isoforms are soluble. The human endothelial NOS gene has been cloned. It has several highly repetitive regions which could provide potential sites for DNA polymorphism. It might be of interest to examine the relationship between such polymorphism and cardiovascular disorders.

Amino Acid Oxidoreductases↗
PubMed1994

Fc epsilon RI-stimulated Ca(2+)-dependent secretion from rat basophilic leukemia (RBL-2H3) cells permeabilized with Staphylococcal alpha-toxin: Fc epsilon RI-operated signals are not mimicked by the actions of GTP gamma S.

1. RBL-2H3 cells permeabilized with alpha-toxin responded to dinitrophenol (30-40 mol/mol)-conjugated human serum albumin, as antigen, to secrete [14C]serotonin in the micromolar range of free Ca2+. 2. Calcium ion alone did not cause substantial secretion. 3. Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) (100 microM) in combination with Ca2+ produced only negligible [14C]serotonin secretion. 4. GTP gamma S, in the presence of cytochalasin D, caused optimal secretion of [14C]serotonin in a Ca(2+)-dependent manner.

Adenine↗
PubMed1994

Linkage analysis of BRCA1 in Japanese breast cancer families.

We examined the involvement of BRCA1, which plays a major role in Western breast cancer families, in Japanese breast cancer families. Eleven families, in which at least three individuals within third degree relatives were affected by breast cancer, were collected. Five of them were early-onset breast cancer families, in which the average age at diagnosis was less than 45 years, and the other six were late-onset families. Ovarian cancer was observed in one patient in the early-onset families. Using seven polymorphic markers on chromosome 17q21, D17S250, ERBB2, THRA1, D17S579, D17S588, GIP and NME1, linkage to BRCA1 was analyzed. Linkage was not detected in any single family. Assuming homogeneity in an inherited component that confines the susceptibility to breast cancer in all families, we summed the LOD scores of all families. The cumulative LOD score obtained was -1.86 for D17S588 at theta = 0.001, indicating no linkage with BRCA1. Since the proportion of families linked to BRCA1 is larger in Western early-onset breast cancer families than in late-onset ones, we also summed the LOD scores of five early-onset families. However, again a negative LOD score was obtained. These results suggest that BRCA1 is not a major breast cancer susceptibility gene in Japanese familial breast cancer.

Adult↗
PubMed1994

Identification of monocyte chemotactic factors in supernatants of ovalbumin-stimulated lymphocytes from patients with atopic dermatitis who are sensitive to hen's egg.

Monocyte chemotactic activities in supernatants of ovalbumin (OA)-stimulated peripheral blood mononuclear cell (PBMC) cultures were studied in patients with atopic dermatitis (AD) who were sensitive to hen's egg. The monocyte chemotactic activities in hen's egg-sensitive AD patients were significantly higher than those of non-atopic healthy controls and patients with immediate allergic symptoms. However, the monocyte chemotactic activities were not detected in bovine serum albumin-stimulated PBMC culture supernatants in patients with AD who were sensitive to hen's egg, but not to cow's milk. Furthermore, there was significant correlation between the monocyte chemotactic activities and proliferative responses of PBMCs to OA in hen's egg-sensitive AD patients, whereas there was no significant correlation between the monocyte chemotactic activities and radioallergosorbent test values. These results suggest that PBMCs stimulated with food antigens produce monocyte chemotactic factors which relate to the pathogenesis of AD in food-sensitive AD patients and that the pathogenesis of AD may be related to cell-mediated immune responses.

Adolescent↗
PubMed1994

Role of cyclic AMP-induced Cl conductance in aqueous humour formation by the dog ciliary epithelium.

1. The effects of isoprenaline, a forskolin derivative NKH-477, and dibutyryl cyclic AMP (db cyclic AMP) on the membrane potential, conductance and cell volume of the dog non-pigmented ciliary epithelium (NPE) were investigated by intracellular potential recording, nystatin-perforated patch clamp technique and videomicroscopic cytometry. 2. The resting membrane potential of NPE was about -70 mV in physiological saline and was depolarized by isoprenaline in a dose-dependent manner with an ED50 of about 3 nM. This depolarization was competitively antagonized by the beta-adrenoceptor antagonist, timolol (pA2 = ca. 9) and almost completely blocked by the Cl transport blocker, DIDS. 3. In single dissociated NPE cells, 10 microM isoprenaline induced an inward current and caused a concomitant decrease in cell volume. The reversal potential measurement indicated that this inward current was carried mainly by Cl ion. DIDS (10 microM) abolished both the current and cell volume decrease. 4. NKH-477 (10 microM) or db cyclic AMP (1 mM) also induced an inward current together with a cell volume decrease, the properties of which were similar to those caused by isoprenaline. 5. These results suggest that beta-adrenoceptor stimulation in NPE leads to an increased rate of aqueous humour production by increasing Cl- efflux via an elevation of cyclic AMP and this effect is efficiently blocked by timolol.

Animals↗
PubMed1994

Contraction and depolarization induced by fetal bovine serum in airway smooth muscle.

We investigated the effects of fetal bovine serum (FBS) on the resting membrane potential and muscle tone of canine airway smooth muscles using tension recording and microelectrode methods. At concentrations > 0.1%, FBS induced a sustained increase in muscle tone. At concentrations > 1%, FBS depolarized the resting membrane potential of dog trachea in a dose-dependent manner. When FBS was dialyzed, it failed to induce a sustained increase in muscle tone or to depolarize the membrane, indicating that FBS contained factor(s) that induced contraction of dog airway smooth muscles. When FBS was dialyzed against distilled water, the outer solution which was freeze dried and then reconstituted (> 1% in original vol) induced a sustained increase in muscle tone, indicating that FBS contained dialyzable factor(s) that increased muscle tone and depolarized the resting membrane potential of dog airway smooth muscles. Methysergide (10(-6) M) or cyproheptadine (10(-6) M), nonspecific antagonists to serotonin receptors, 5-hydroxytryptamines (5-HT1 and 5-HT2), markedly reduced the FBS-induced increase in the muscle tone to approximately 20% of the original value but did not abolish the response. On the other hand, methysergide (10(-6) M) completely suppressed the increase in the muscle tone evoked by peak fractions obtained by application of the dialysate of FBS or 5-HT to a C18 reverse-phase column, indicating the peak fractions contained only 5-HT. These observations indicate that FBS contained 5-HT and an unknown factor(s) responsible for increase in the muscle tone of the airway smooth muscle induced by FBS.

Animals↗
PubMed1994

Effects of epithelial cell supernatant on membrane potential and contraction of dog airway smooth muscles.

We investigated the effects of cultured epithelial cells and supernatants on resting membrane potential and excitatory neuroeffector transmission in smooth muscle cells of dog trachea and bronchioles. The mean resting membrane potential of the mucosa-free tracheal smooth muscle cells was -59.5 +/- 1.5 mV (+/- SD). Application of cultured epithelial cells (> 2.5 x 10(5) cells/ml) hyperpolarized the membrane, resulting in a potential of -64.5 +/- 1.7 mV. The supernatant of the cultured epithelial cells also increased the resting membrane potential of the mucosa-free tracheal smooth muscle cells by 4 to 9 mV. These hyperpolarizing actions were not modified by indomethacin (10(-5) M), l-NG-nitroarginine (10(-5) M), or oxyhemoglobin (10(-5) M), but were inhibited by glibenclamide (10(-6) M). The supernatants of the cultured epithelial cells completely or partially suppressed the contractile response of epithelium-denuded bronchioles to electrical field stimulations and suppressed the amplitude of excitatory junction potentials of the trachealis evoked by electrical field stimulations. Indomethacin prevented the inhibitory effect of supernatants on the amplitude of twitch contractions and excitatory junction potentials and markedly suppressed supernatant-associated inhibition of the excitatory neuroeffector transmission. Furthermore, indomethacin with AA861, a lipoxygenase inhibitor, completely suppressed this effect. Our findings suggest that cultured airway epithelial cells spontaneously release at least two factors. One factor selectively modulates the resting membrane potential, and the other inhibits the excitatory neuroeffector transmission.

Animals↗
PubMed1994

Frontal midline theta rhythm: differentiating the physiological theta rhythm from the abnormal discharge.

The theta rhythm that appears in the frontal midline was studied morphologically and clinically in EEGs performed on 788 patients and 161 normal subjects in their late teens or older. This theta rhythm was classified into 2 types. The Type 1 theta rhythm appeared in short bursts maximally in the Fz lead and spread mainly to the anterior region. It had a high frequency, low voltage and regular waveform. The Type 2 theta rhythm appeared in long runs maximally in the Fz lead and spread mainly to the posterior areas. It had a relatively low frequency, high voltage and irregular waveform. Type 1 was observed in a younger age group (mean age: 20.3 years) that was comprised of healthy subjects and one mentally retarded patient. In no case was the Type 1 theta rhythm accompanied by a paroxysmal EEG abnormality. We therefore believe that Type 1 is a physiological EEG activity (Fm theta). On the other hand, Type 2 was observed in a relatively older age group (mean age: 30.7 years) comprised of patients diagnosed as having epilepsy or intractable headaches. Five of 9 cases showed epileptic EEG abnormalities. We therefore believe that Type 2 might have clinical significance in diagnosis of epilepsy and other cerebral dysfunctions. The EEG pattern that we call the frontal mid-line theta rhythm may be either a physiological theta rhythm or an abnormal discharge. It is possible to determine whether the theta rhythm is the former or the latter, and we believe this differentiation to be clinically important.

Adolescent↗
PubMed1994

[Middle cerebral artery occlusion with unilateral moyamoya like vessels and with ruptured anterior cerebral artery aneurysm--its relation to the antiphospholipid antibody syndrome].

We report a case of right middle cerebral artery occlusion associated with ipsilateral basal moyamoya like vessels and ruptured anterior cerebral artery aneurysm. A 59-year old man suddenly developed a consciousness disturbance and was brought to our hospital by ambulance. On admission, computed tomography (CT) of the head revealed a diffuse dense high-density lesion in the basal cistern and in the bilateral sylvian fissures, and a round homogeneous high-density area in the interhemispheric fissure. Subsequent angiography showed a large anterior cerebral artery aneurysm and occlusion of the right middle cerebral artery with moyamoya-like vessels. We made a diagnosis of subarachnoid hemorrhage due to aneurysm rupture. An emergency bifrontal free bone craniotomy was performed, utilizing the interhemispheric approach and the neck of the aneurysm was clipped. On the 68th postoperative day the patient was ambulatory and discharged from the hospital. Hemodynamic stress was thought to be the main cause of the anterior cerebral artery aneurysm. Because the laboratory data on admission included a false-positive serological test for syphilis, we tested the patient for antiphospholipid antibodies, and repeatedly found anticardiolipin antibody in the patient's serum. The antiphospholipid antibody syndrome may have been responsible for the occlusion of the middle cerebral artery, in this patient and we think that testing for serum antiphospholipid antibodies is important in occlusive cerebral artery disease, especially in moyamoya disease or when moyamoya-like vessels are present.

Aneurysm, Ruptured↗
PubMed1994

IgG subclass levels and southern analysis of DNA in primary immunodeficiency diseases including IgG subclass deficiency.

Serum IgG subclass levels are reported for twenty patients with primary immunodeficiency diseases, including four patients with IgG subclass deficiency, using an enzyme-linked immunosorbent assay with monoclonal antibodies. The disorder of each patient with IgG subclass deficiency seemed to be heterogeneous immunologically and clinically. One had complete IgG2-IgG4 deficiency, another had IgG2-IgG4-IgA deficiency and the other two had IgG2-IgA deficiencies. We did not find any structural-gene deletions in the constant region of the human immunoglobulin heavy-chain locus. Although the possibility of defects in genes controlling immunoglobulin expression, or small mutations, remains, these results suggest that IgG subclass deficiency is not always linked to particular structural-gene deletions.

Adolescent↗
PubMed1994

[A case of the localized fibrous mesothelioma which size decreased temporarily].

A 46-year-old woman complained of a back pain and was pointed the abnormal shadow on chest X-ray by the physician, so she consulted our hospital in January 1987. After a few weeks, the size of the shadow decreased with no treatment, then we followed up her with roentgenograms. Since '91, its size had increased again. Needle biopsy did not give us the diagnosis, but we performed the operation because we suspected some malignant disease. We resected the tumor with the enough surgical margin. Its size was 4 x 3 x 3 cm, its surface was white and smooth. Its was elastic hard and had the pedicle which jointed the visceral pleura. Histological diagnosis was the localized fibrous mesothelioma.

Female↗
PubMed1994

[A resected case of sporadic myxoma of the right ventricle: the diagnosis was supported with DNA flow cytometry].

We report a rare case of a 16-year-old male who had myxoma originating from septal band of the right ventricle. His ECG anomaly was found incidentally upon a physical examination. Subsequently, echocardiography and angiocardiography demonstrated a tumor occupying the right ventricular outflow tract and protruding into the main pulmonary artery in systolic phase. He was operated upon using extracorporeal circulation. By right ventriculotomy the tumor was resected together with septal tissue 5 mm around the stalk, which branched into the myocardium. The defect was closed using mattress sutures with Dacron felt strips. We also analyzed the DNA content of the tumor. The DNA flow cytometry yielded a single cell population with diploid DNA content. This result showed that the tumor is sporadic form of cardiac myxoma. His postoperative course was uneventful. Thirty months after the surgery, patient has no sign of recurrence. The DNA flow cytometry is helpful for detecting clinical behavior of the cardiac myxoma, because microscopic examination can not readily distinguish sporadic myxoma from so-called complex myxoma.

Adolescent↗
PubMed1994

Expression of VpreB gene in common variable immunodeficiency.

We analyzed the expression of the VpreB gene in 5 common variable immunodeficiency (CVI) patients. There was no deletion or large mutation as compared with control DNA by Southern blotting. In the peripheral blood mononuclear cells of CVI patients, expression of the VpreB gene was not detected by polymerase chain reaction. These results suggest that there were no immature B cells such as pro- or pre-B stages in the peripheral blood mononuclear cells of these CVI patients. In B lymphoblastoid cell line (LCL) cells, expression of VpreB gene was observed in patients and Manca cells. The results suggest that the stages of these LCL cells may be a traditional stage between pre-B and mature B cell. As for the Manca cell, our result is in accordance with a recent report that surface immunoglobulin-positive cell lines also express the pre-B-related genes.

B-Lymphocyte Subsets↗
PubMed1994

[A case of UIP with autoimmune hemolytic anemia].

A 70-year-old male was admitted because of cough and sputum. Chest X-ray showed bilateral interstitial shadows, and usual interstitial pneumonitis was diagnosed by TBLB and BAL. He was followed without medication. The dyspnea increased and the abnormal shadow spread on chest X-ray. Autoimmune hemolytic anemia was newly diagnosed because the RBC count was 195 x 10(4)/mm3, Hb was 8.6 g/dl, and direct Coombs test and warm antibody were positive. In this case, there appears to be a relationship between deterioration of interstitial pneumonia and the on-set of autoimmune hemolytic anemia.

Aged↗