Biomedical subjects

R Inoue

Publications and source records attributed to R Inoue.

At least 127 records · Page 7Linked to original sources

PubMed1995

Role of nitric oxide in non-adrenergic, non-cholinergic relaxation and modulation of excitatory neuroeffector transmission in the cat airway.

1. The effects of nitrosocysteine (cys-NO), L-N omega-nitroarginine (L-NNA) and L-N omega-nitro-L-arginine methylester (L-NAME), oxyhaemoglobin and Methylene Blue were observed on the resting membrane potential, muscle tone and excitatory junction potentials (EJPs) of cat tracheal smooth muscle tissue. 2. Cys-NO (10(-9) to 10(-6) M) showed no effect on the resting membrane potential of smooth muscle cells of the cat trachea but it dose-dependently relaxed the tracheal tissue in the presence of 5-HT, atropine and guanethidine. 3. Electrical field stimulation (EFS) applied during contraction evoked by 5-HT in the presence of atropine and guanethidine evoked non-adrenergic, non-cholinergic (NANC) muscle relaxation. L-NNA (10(-4) M) and L-NAME (10(-4) M) completely suppressed the relaxation when single or short repetitive stimuli were applied, but suppression was incomplete with repetitive stimuli of 4 ms pulse duration applied at 20 Hz. A substantial part of the L-NNA- or L-NAME-insensitive relaxation was abolished by tetrodotoxin. 4. Cys-NO dose-dependently suppressed the EJPs without changing the resting membrane potential, and L-NNA, L-NAME, Methylene Blue and oxyhaemoglobin enhanced the amplitude of the EJP to 1.2-1.5 times the control value. 5. EJPs showed some summation when repetitive field stimulation was applied at 20 Hz. L-NNA or L-NAME enhanced the summation, and the mean slopes were increased from 0.61 +/- 0.22 to 2.0 +/- 0.3, or 1.9 +/- 0.2 mV per stimulus. Vasoactive intestinal polypeptide (VIP) antiserum and VIP antagonists further enhanced the summation in the presence of L-NNA. 6. These results indicate that NANC relaxation can be classified into two different components according to the threshold for activation, and nitric oxide is involved in one. The present results also suggest that endogenous or exogenous nitric oxide has a prejunctional action in inhibiting excitatory neuroeffector transmission in addition to a direct action on the smooth muscle cells, presumably by suppressing transmitter release from the vagus nerve.

Animals↗

PubMed1995

Long-term prognosis after thrombolytic therapy for acute myocardial infarction.

In order to clarify the relationship between the patency of the infarcted arteries and subsequent long-term prognosis after thrombolytic therapy, we evaluated 116 patients with acute myocardial infarction treated with intracoronary (112 patients) or intravenous (four patients) urokinase. Patients treated with angioplasty after thrombolysis were excluded. The infarcted vessel was recanalized in 52 patients (patent group) and was not in the remaining 64 patients (occluded group). Five-year and 8-year follow up was conducted in 91% and 81% of the patients, respectively. The 1-, 5- and 8-year survival rate for the patent and occluded group was 91.8 and 80.9%, 80.8 and 79.2%, and 75.9 and 75.6%, respectively. The survival rate in the patent group tended to be higher than that in the occluded group up to 4 years. However, after 5 years, both groups showed similar survival rates. Therefore, reopening of the infarcted arteries with thrombolysis was not an independent predictor for late cardiac death (Cox regression analysis).

Aged↗

PubMed1995

A preliminary study on plasma concentrations of bifemelane, indeloxazine and propentofylline in aged patients with organic brain disorders.

1. Plasma concentrations of cerebral metabolic activating drugs (bifemelane, indeloxazine and propentofylline) were studied in 68 patients (male 25, female 43) with dementia or other organic brain diseases. 2. The variations in plasma concentrations of these drugs were much bigger than expected. Measurements of bifemelane level with time course also disclosed that the concentrations were relatively stable for several months, but they varied very much among patients. 3. These findings suggest that drug monitoring are important in terms of evaluation of drug efficacy and prevention of side effects.

Aged↗

PubMed1995

A juvenile case of frontotemporal dementia: neurochemical and neuropathological investigations.

1. An autopsy case of frontotemporal dementia with onset at the early age of 28 years is reported. 2. The neuropathological features consisted of limited, knife-like frontotemporal atrophy with severe neuronal loss, spongiform change and gliosis, which is compatible with the frontotemporal dementia. 3. Biochemical determinations disclosed that biogenic amines and their metabolites, predominant in the dopaminergic markers, were depleted in the damaged regions. 4. Since biochemical data in frontotemporal dementia are few in previous studies, it will be determined whether these biochemical changes are characteristic for the juvenile type of frontotemporal dementia or not.

Adult↗

PubMed1995

Carbachol-induced desensitization of rat basophilic leukemia (RBL-2H3) cells transfected with human m3 muscarinic acetylcholine receptors.

1. Carbachol-induced homologous desensitization of the secretory response was investigated by transfecting RBL-2H3 cells with cDNA encoding the human m3 muscarinic acetylcholine receptor (RBL-m3). 2. Exposure of RBL-m3 cells to 100 microM carbachol for 30 min in Ca2+-free medium inhibited the secretion induced by the subsequent addition of 10 microM carbachol plus Ca2+. 3. Desensitized cells bound [3H]quinuclidinyl benzilate with a similar Bmax and Kd to those of control cells. 4. The carbachol-induced transient increase in levels of inositol 1,4,5-trisphosphate was not changed by desensitization. 5. Homologous desensitization persisted when desensitized cells were permeabilized with Staphylococcal alpha-toxin.

Animals↗

PubMed1995

Genetic polymorphisms and susceptibility to cancer development.

Humans show heterogeneous susceptibility to cancer development, suggesting the involvement of various genetic backgrounds in control of the production of endogenous carcinogens, the metabolism of carcinogens, the repair of DNA damage, cell proliferation and defence mechanisms including immune reactions. Gastric cancer is the major cancer in Japan. However, little is known about the genes linked with its development. In 1967, we found that N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced gastric cancers in Wistar rats. Subsequently the Buffalo strain of rats was reported to be resistant to MNNG stomach carcinogenesis, while ACI rats were very sensitive. In a carcinogenesis study using F1 and F2 rats, we suggested that this trait of MNNG stomach carcinogenesis-resistance was regulated by a single autosomal dominant allele. The O6-methylguanine adduct levels in gastric mucosa induced by MNNG were the same in Buffalo and ACI rats, but cell proliferation induced by MNNG was much higher in ACI than Buffalo animals. Chromosome mapping of the gene responsible for susceptibility to MNNG-induced carcinogenesis is now in progress and its identification will hopefully give us clues to the involvement of genetic traits in susceptibility to gastric cancer in humans. In addition, the genetic background of susceptibility to breast cancer is also being studied. In Japan, about 5% of all cases of breast cancer are familial. We have studied BRCA1, the breast cancer susceptibility gene, as a determinant of susceptibility to breast cancer by linkage analyses in 11 families, but our results indicate that BRCA1 may not be important for development of familial breast cancer in Japanese.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Failure of IgG production due to a defect in the opening of the chromatin structure of I gamma 1 region in a patient with IgG and IgA deficiency.

Patients with common variable immunodeficiency (CVID) display reduced levels of two or all three of the major immunoglobulin isotypes, and the deficiency is characterized by failure of B cells to differentiate into plasma cells in many cases. A patient (14 years old, female) showed normal serum IgM levels and low serum IgG and IgA levels, including low levels of all IgG subclasses. Northern blot analysis suggested that the patient's B cells may be defective at the immunoglobulin heavy chain isotype switch. The germ-line C gamma 1 transcript was amplified from cDNA of healthy controls by the addition of recombinant IL-2 (rIL-2) to pokeweed mitogen-stimulated peripheral mononuclear cells or Staphylococcus aureus Cowan I (SAC)-stimulated IgM-producing lymphoblastoid cell lines (LCL) transformed by Epstein-Barr virus, while it was not amplified from cDNA of the patient. In the I gamma 1 region of LCL cultured with SAC plus rIL-2, the inner cytosine in the 5' C-C-G-G 3' sequence nearest the 3' site of the I gamma 1 region, at least, was not completely unmethylated in the patient. Moreover, the DNase I hypersensitive site was not induced in the patient's LCL by SAC plus rIL-2. These results indicate that the defects of the immunoglobulin heavy chain isotype switch in the patient's B cells are due to failure in the synthesis of germ-line C gamma transcripts, and this may be caused by defects in opening of the chromatin structures of specific switch regions.

Adolescent↗

PubMed1995

IgG2 deficiency associated with defects in production of interferon-gamma; comparison with common variable immunodeficiency.

We report a novel mechanism of IgG2 deficiency. Several investigators have reported patients with IgG subclass deficiencies due to homozygous deletion of immunoglobulin heavy chain constant region genes. However, it is unclear what mechanism is responsible for IgG subclass deficiency in cases where no gene deletions have been detected and which are accompanied by recurrent infections due to aberrant immunoregulation. In the present study, we have focused our attention on production by peripheral blood mononuclear cells (PBMCs) of interferon-gamma (IFN-gamma), which is known to induce IgG2 expression. PBMCs from four patients with IgG2 deficiency and their families were studied. Mitogeninduced IFN-gamma production by PBMCs was decreased in all of the patients, although the proliferative responses of PBMCs and the percentages of CD3, CD4, and CD8 T cell subsets were not decreased. IgG2 production by PBMCs was restored upon addition of IFN-gamma and mitogen to the PBMCs of the patients with IgG2 deficiency though it was not restored in the patients with common variable immunodeficiency. We conclude that defects in production of IFN-gamma play an important role in IgG2 deficiency.

Adult↗

PubMed1995

Aberrant patterns of immunoglobulin levels in Wiskott-Aldrich syndrome.

We have investigated IgM deficiency in Wiskott-Aldrich syndrome patients. From the assessment of T and B cell functions in pokeweed mitogen-induced immunoglobulin (Ig) production, IgM deficiency was chiefly thought to result from B cell dysfunction. The percentages of surface IgM-bearing cells were decreased in peripheral blood mononuclear cells (PBMCs) and the number of IgM-secreting cells was also decreased. Lymphoblast cell lines (LCLs) from the patients have produced IgG and IgA, but never IgM. Moreover the expression of the C mu transcript from the patients' PBMCs and their LCLs were decreased, whereas the C gamma gene was well expressed. No germ-line polymorphism existed between the patients and the controls in the C mu region, and no mutation was detected in the mu s C-terminal and the M exon by nucleotide sequencing. These suggest that the Ig heavy chain (IGHC) isotype switch may be abnormally accelerated in the patients' B cells. While the methylation patterns of the human Ig enhancer gene region were the same between the patient and the control, the methylation patterns of the I gamma 1 region showed less methylation in the patient than in the control, which may cause low IgM expression and high expression levels of other classes located downstream of the IGHC gene.

Adolescent↗

PubMed1995

Extracellular H+ modulates acetylcholine-activated nonselective cation channels in guinea pig ileum.

The effects of external H+ on the acetylcholine-induced inward current (nonselective cationic current; InsACh) in guinea pig ileal smooth muscle were investigated using the conventional whole cell patch-clamp technique. When the external pH (pHo) was lowered, the amplitude of InsACh was increased, with no significant change in the reversal potential or no detectable induction of other ionic permeabilities. The dose-response curve for this effect was best described by a Hill-type equation with an apparent pKa value of 7.4 and a Hill coefficient of approximately 1. The effect of pHo was associated with a shift of the steady-state activation curve for InsACh; the half-maximum activation potential became more negative on lowering pHo. Similar results were obtained when InsACh was activated by intracellularly applied guanosine 5'-O-(3-thiotriphosphate). These results indicate that the external H+ activity is an efficient regulator of InsACh channel, and this may have a physiological importance for controlling the muscarinic receptor-mediated contractions in this muscle.

Acetylcholine↗

PubMed1995

Genetic analysis of IgE and the IGHE, IGHEP1 and IGHEP2 genes in atopic families.

The familial occurrence of allergic diseases was studied in 478 individuals and their family members. The results showed that there was pronounced familial clustering. Total serum IgE concentrations of atopic patients and their parents were well correlated. Moreover, the concentration of specific IgE of the patients and their parents was also well correlated, suggesting that IgE production was genetically determined. To determine if major structural abnormalities of IGHE, IGHEP1 and IGHEP2 genes might lead to aberrant control and subsequent increase in IgE concentration, genomic DNAs from 55 individuals, i.e., 31 atopic patients and their family members, were examined. We detected the IGHE, IGHEP1 and IGHEP2 genes in all 55 leukocyte DNAs. We could not find any large deletions or duplications in the IGHE, IGHEP1 and IGHEP2 genes of atopic patients with high serum IgE concentrations.

Adolescent↗

PubMed1995

[Biophysical and pharmacological characterization of receptor-operated nonselective cation channels (ROCC) and their regulatory mechanisms in smooth muscle].

Stimulation of excitatory receptors in smooth muscle often leads to the opening of ROCC. These channels exhibit considerable permeability to Ca2+, and they have been regarded as the most probable candidate for the "receptor-operated Ca2+ entry" pathway. The muscarinic receptor ROCC in guinea pig ileum (mROCC) have a unitary conductance of -25pS and are activated through a pertussis toxin-sensitive G protein. mROCC permeate Ca2+ and Ba2+ several fold more preferably than monovalent cations, and they are inhibited by various types of K channel blockers, diphenylamine-2-carboxylate derivatives and even by nicardipine and D-600 at high concentrations. mROCC are efficiently regulated by various physiological factors including the membrane potential, intracellular Ca2+ concentration, external pH and osmolarity. The effective ranges of these factors span their dynamic ranges under physiological conditions. In addition to these properties, mROCC have several sites sensitive to external polyvalent cations. The alpha 1-adrenergic receptor ROCC in rabbit portal vein resemble mROCC in many respects, e.g., the unitary conductance, ionic selectivity, activation kinetics, sensitivity to polyvalent cations and voltage-dependence. These complex characteristics of ROCC suggest that they play other roles in addition to being just a passive cation permeable pore in agonist-mediated Ca2+ mobilization in smooth muscle.

Animals↗

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↗