Biomedical subjects

R Inoue

Publications and source records attributed to R Inoue.

At least 145 records · Page 8Linked to original sources

PubMed1995

Cerebral gumma showing linear dural enhancement on magnetic resonance imaging--Case report.

A 51-year-old male presented with a rare cerebral gumma accompanied by abducens nerve paresis and cerebellar infarction. Magnetic resonance (MR) imaging demonstrated a homogeneous enhance mass lesion and adjacent linearly enhanced dura mater. Histological examination of the mass revealed a caseating granuloma. Serological studies were positive for active syphilis. Although linear dural enhancement adjacent to the mass lesion on MR imaging is characteristic of meningioma, this finding is also demonstrated in cerebral gumma. Therefore, cerebral gummas should also be included in the differential diagnosis. Immunological tests for syphilis (serum, cerebrospinal fluid) can confirm the diagnosis.

Abducens Nerve↗

PubMed1995

Endoscopic sclerotherapy in a rat model of esophageal varices.

BACKGROUND: Partial ligation of the portal vein has been shown to induce not only prehepatic portal hypertension but also esophageal varices in the rat. We developed an esophageal endoscopic system for endoscopic sclerotherapy of esophageal varices in rats. In the present study the efficacy of three sclerosing agents, 1% polidocanol, 5% ethanolamine oleate, and 99.5% ethanol, was compared, using this model. METHODS: Sclerosing agents were injected paravariceally in 42 rats with partial portal vein ligation. Their efficacy was compared endoscopically and histologically. RESULTS: Ethanol induced the most severe ulcers and subsequent stricture formation. The damage induced by 1% polidocanol was mild and healed quickly, whereas 5% ethanolamine oleate induced moderate damage. The varices disappeared because of fibrosis that developed after ulceration. CONCLUSIONS: The results were consistent with the known properties of these three agents, suggesting that the esophageal endoscopic system for sclerotherapy in rats provides a useful method for experimental studies of sclerotherapy.

Animals↗

PubMed1995

Expression of surrogate light chain in common variable immunodeficiency.

VpreB and lambda-like genes encode proteins that can associate to form a light-chain-like structure, the surrogate light chain (SLC). VpreB and lambda-like genes are selectively expressed in human progenitor B and precursor B (pre-B) cells. We analyzed the expression of VpreB and lambda-like genes in seven patients with common variable immunodeficiency (CVI). Gene expression was examined in the peripheral blood mononuclear cells (PBMCs) using the polymerase chain reaction. In four CVI patients, two of whom were brothers, the expression of the VpreB gene was detectable in the PBMCs. In the brothers with CVI, the expression of the VpreB gene was also examined in bone marrow cells, where it was found to be expressed in trace amounts. A number of the brothers' bone marrow cells were stained with mu and kappa antibodies using the avidin-biotin complex method. In lambda 5-gene-deleted mice, B cell development in the bone marrow is blocked at the pre-B stage, but the blockade is leaky. We suggest that expression of the SLC is weak in patients with CVI compared with their normal counterparts, and this may be one of the underlying mechanisms of CVI.

Adult↗

PubMed1995

Effects of interferon-alpha on L-BCGF- and TNF-alpha-induced proliferation of hairy cell leukemia in Japan.

Interferon-alpha (IFN-alpha) is very effective in patients with hairy cell leukemia (HCL), although its mechanism of action is still unknown. To investigate this issue, we studied the in vitro response to IFN-alpha of a variant type of HCL, recently reported by us as the Japanese variant. Their clinical response to IFN-alpha (remission rate 35.7% in the multicenter study in Japan) was inferior to that of typical HCL (remission rate 80%; mean of previous reports). We found that both low molecular weight B-cell growth factor (L-BCGF) and tumor necrosis factor-alpha (TNF-alpha) induced the proliferation of HC from patients with the Japanese variant, as well as those with typical HCL. While, in typical HCL, IFN-alpha strongly inhibited the in vitro proliferation of HC induced by L-BCGF and TNF-alpha, the inhibitory effect of IFN-alpha on L-BCGF and TNF-alpha-induced proliferation was low in most Japanese variant patients. These in vitro findings may be related to the extent of clinical efficacy of IFN-alpha in the Japanese variant, obtained in the multicenter study. Since the degree of inhibition was parallel in L-BCGF- and TNF-alpha-induced proliferation in three patients examined simultaneously, it appeared that the antiproliferative effect of IFN-alpha is not specific to individual growth factors. Rather, IFN-alpha might affect fundamental growth mechanisms triggered by these factors.

Cell Division↗

PubMed1995

[Familial breast cancer].

Japanese breast cancer families were collected and classified into the following 7 types according to the onset age and the distribution of other cancers in the family lines; early-onset type, late-onset type, familial breast-ovarian cancer type, familial breast-prostate cancer type, familial breast-thyroid cancer type, familial male and female breast cancer type and multiple primary cancer type. We have detected no p53 germ line mutations in the patients from these families. Linkage with BRCA1 was not detected in any single families. These data indicate that neither BRCA1 or p53 is a major susceptible gene in Japanese familial breast cancer. However, in the two site-specific breast cancer families, the same nonsense mutation of the BRCA1 gene was detected.

Age of Onset↗

PubMed1995

Genetic alterations in HCA-induced tumors.

Accumulating evidence from molecular oncology indicates that carcinogens may induce tumors through characteristic mutations in characteristic genes for each agent. Identification of specific mutations induced by heterocyclic amines (HCAs), food-borne carcinogens, should facilitate risk assessment of HCAs in man. Identification of characteristic genes affected by HCAs will lead to identification of the genes involved in human carcinogenesis. We therefore examined tumors induced by various HCAs from these two viewpoints. With regard to forestomach tumors induced in CDF1 mice by 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), mutations of Ha-ras and p53 were observed in four of eight and two of four tumors, respectively. One papilloma examined had mutations in both Ha-ras and p53, whereas two carcinomas had only one or the other. For Zymbal gland tumors induced in F344 rats by IQ, mutations of Ha- or Ki-ras were observed in both of two papillomas and in 10 of 13 squamous cell carcinomas (SCCs), while p53 mutations were limited to only four of the SCCs. The ras mutation was thus suggested to be an early event, while p53 mutation was more associated with malignancy. In liver tumors induced in F344 rats by 2-amino-3,8-dimethylimidazo[4, 5-f]quinoxaline (MeIQx), mutations of p53 were observed in one of two moderately-differentiated and two of two poorly-differentiated hepatocellular carcinomas (HCCs). No such changes were found in any of nine well-differentiated HCCs, suggesting p53 mutation to be a very late event. In colon tumors induced in F344 rats by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (nine adenocarcinomas), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) (two adenomas and nine adenocarcinomas), or 2-amino-6-methyldipyrido[1,2-a:3', 2'-d]imidazole (Glu-P-1) (seven adenocarcinomas), a Ki-ras mutation was found in only one Glu-P-1-induced adenocarcinoma. No p53 mutations could be detected. In mammary gland carcinomas induced in F344 rats by PhIP, Ha-ras was activated in three of 17 carcinomas and p53 was mutated in one of 10 carcinomas. We therefore concluded that other genes were involved in colon and mammary carcinomas. G:C base pairs were involved in all 42 positive cases of the present study, and 36 of them were guanine base mutations. This indicates that the changes in IQ, MeIQx, PhIP and Glu-P-1 tumors were mainly caused by non-transcribed strand modifications through their major DNA adducts, N2-(guanin-8-yl)HCAs. Ha-ras mutations in the forestomach tumors induced by MeIQ were all G to T transversions at the second position of codon 13. Mutation sites of p53 did not appear to be specific in the forestomach, Zymbal gland and liver tumors.

Animals↗

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↗