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Biomedical subjects

R Inoue

Publications and source records attributed to R Inoue.

At least 163 records · Page 9Linked to original sources

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↗

[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↗

Hairy cells from hairy cell leukemia patients presenting with pronounced polyclonal hypergammaglobulinemia secrete a factor enhancing IgG synthesis.

We studied the immunological function of hairy cells from hairy cell leukemia (HCL) patients presenting with pronounced polyclonal hypergammaglobulinemia (PPH). Hairy cell conditioned medium (HCCM) obtained from HCL patients with PPH augmented IgG production by normal peripheral blood mononuclear cells in a dose-dependent fashion, while HCCM from patients without PPH had no effect on IgG production. HCCM from the patients with PPH failed to enhance IgG synthesis by T cell-depleted mononuclear cells. Separation of T and B cells by a 0.4-microns membrane as well as monoclonal antibodies to HLA-DR and CD3 molecules prevented HCCM-dependent IgG synthesis. No B cell growth factor activity, interleukin-1, or interleukin-6 was detected in the HCCM. On examination by fractionation of the HCCM, IgG-inducing activity was detected in the fractions of 5000 to 8000 Da. These results indicate that hairy cells from HCL patients with PPH secrete a factor inducing IgG synthesis, and that the induction of IgG synthesis by the factor requires T-B cell interactions involving T cell receptor/CD3 complex and MHC class II antigens. This factor may play an important role in the development of PPH.

B-Lymphocytes↗

Physiology of muscarinic receptor-operated nonselective cation channels in guinea-pig ileal smooth muscle.

Stimulations of autonomic nerves in smooth muscle often evoke both fast and slow excitatory junction potentials (EJPs), which are thought to involve activations of several distinct types of nonselective cation channels (NSC channels). The ACh-activated NSC channel in guinea-pig ileum (I(ns), ACh) is one probably responsible for the slow EJP and seems to undergo various regulations. This short paper will review the physiology of I(ns),ACh, with particular emphasis on its dynamic interactions with other physiologically important factors such as the membrane potential, [Ca2+]i and pH.

Acetylcholine↗

Secondary spontaneous pneumothorax.

To assess the clinical manifestations and therapy of secondary spontaneous pneumothorax (SSP), 123 episodes of SSP in 67 patients were retrospectively reviewed and were compared with 254 episodes of primary spontaneous pneumothorax in 130 patients. The major underlying lung diseases associated with SSP were emphysema (22 patients) and tuberculosis (21 patients). The average age of patients with SSP was 66.8 years, and the most common symptom was dyspnea. The average arterial oxygen tension at onset of SSP was 61.1 +/- 12.1 mm Hg (mean +/- standard deviation), which was lower than that of patients with primary spontaneous pneumothorax (p < 0.01). The recurrence rate of open thoracotomy with pleural abrasion was 12.5% (3 of 24 episodes), which was not lower than that of thoracostomy tube drainage with chemical pleurodesis using tetracycline (recurrence rate, 18.8%) (p > 0.5). We concluded that considering the high age of the patients, the presence of underlying lung diseases, and the increased operative risk, thoracostomy tube drainage rather than open thoracotomy was preferred as the first choice of therapy for SSP.

Adolescent↗

Stabilization of inducible nitric oxide synthase by monoclonal antibodies.

We have produced 14 monoclonal antibodies to inducible nitric oxide synthase purified from rat peritoneal cytotoxic activated macrophages. None of the antibodies showed neutralizing activity, but some of them enhanced the enzyme activity through stabilization of the enzyme.

Amino Acid Oxidoreductases↗

Defective calcium-dependent signal transduction in T lymphocytes of ataxia-telangiectasia.

T-cell functions of two patients with ataxia-telangiectasia were investigated. Patients with ataxia-telangiectasia had reduced percentages of circulating CD3+ cells and CD4+ cells, although neither patient had a reduced percentage of circulating CD8+ cells. The proliferative responses and interleukin-2 production of peripheral blood mononuclear cells to T-cell mitogens were reduced in the patients. The intracellular calcium concentration in T cells or CD4+ cells from both patients was only slightly increased after phytohaemagglutinin stimulation. Moreover, the concentration after OKT3 stimulation was not or only slightly increased in T cells or CD4+ cells from both patients. Our results suggest that the functional defect of T cells is caused by defective Ca(2+)-dependent signal transduction through the CD3 complex of the surface in T cells of ataxia-telangiectasia.

Adolescent↗

Expression of secreted immunoglobulin heavy chain genes and immunoglobulin-secreting cells in human lymphocytes.

The numbers of immunoglobulin-secreting cells in peripheral blood mononuclear cells and the expression of mRNA for secreted type of immunoglobulin heavy chains were investigated in healthy children, compared with the percentages of surface immunoglobulin-bearing cells and the expression of mRNA for membrane-bound type of immunoglobulin heavy chains, respectively. Although a difference between expression of mu s mRNA and mu m mRNA was unclear, mu mRNA was well transcribed. The expression of gamma s mRNA or alpha s mRNA was markedly higher than that of gamma m mRNA or alpha m mRNA. However, although the detection methods could be of different sensitivities, the percentage of IgM-, IgG-, or IgA-secreting cells was markedly low, compared with the percentage of surface IgM-, IgG-, or IgA-bearing cells, respectively. Therefore, additional regulation of the pattern of the immunoglobulin gene expression may be exerted at the translational and post-translational stages.

Antibody-Producing Cells↗

Pharmacological characterization of muscarinic receptor-activated cation channels in guinea-pig ileum.

1. The pharmacological properties of cationic currents activated by acetylcholine (ACh) (Icat) in guinea-pig ileal smooth muscle cells were investigated, with conventional single patch electrode or nystatin-perforated whole-cell recording. Cs-aspartate was used as the internal solution to allow selective measurement of Icat. 2. Well-known K channel blockers, tetraethylammonium (TEA), 4-aminopyridine (4-AP), procaine and quinine as well as a Ca releasing agent, caffeine, all produced concentration-dependent inhibition of Icat with rapid onset (time constant approximately 100 ms), when applied externally. The recovery from the inhibition on washout also occurred rapidly in the order of 100 ms except in the case of quinine. Approximate values of the half inhibitory concentrations (IC50) were 10 nM for TEA and caffeine, 1-5 mM for 4-AP and procaine, and 1 microM for quinine. The mode of inhibition was voltage-dependent, i.e., depolarization relieved the inhibition with no change in reversal potential. 3. Externally applied diphenylamine-2-carboxylate (DPC) derivatives, DCDPC and flufenamic acid, produced potent inhibition of Icat at micromolar concentrations (IC50s were < 30 microM for DCDPC and 32 microM for flufenamic acid). The onset of and recovery from inhibition occurred slowly and the degree of inhibition depended on the membrane potential only weakly, without any discernible change in the reversal potential. 4. All of the above-tested drugs exhibited comparable inhibitory actions on the voltage-dependent Ca current in the concentration ranges effective at inhibiting Icat. However, amongst them, quinine and flufenamic acid seemed to have several-fold better selectivity for the Icat channel than for the voltage-dependent Ca channel. 5. Internally dialysed GTPgammaS (100 microM) induced inward cationic currents. The effects of drugs on these currents were similar to their effects on the Icat current.6. These results clearly indicate that many drugs used as pharmacological tools in smooth muscle research exert considerable nonspecific effects on various types of channels. The mechanism of inhibition and the relevance to use of these drugs as blockers for the I cat channel are discussed.

4-Aminopyridine↗

Abnormal responses of common variable immunodeficiency patients' B cells to Staphylococcus aureus Cowan I and interleukin-2.

Responses of common variable immunodeficiency patients' B cells to Staphylococcus aureus Cowan I (SAC) and recombinant interleukin-2 (rIL-2) varied in our study. T-cell function and IL-2 production were normal, and intrinsic B-cell defects were suggested. Some patients showed no increase in expression of IL-2 receptors on B cells with SAC stimulation, which may be due to impaired maturation stages. Two patients showed an increased level of B cells with IL-2 receptors, suggesting blocked development of intracellular mechanisms. One patient may have a defect in immunoglobulin isotype switching.

Adult↗

Dual regulation of cation-selective channels by muscarinic and alpha 1-adrenergic receptors in the rabbit portal vein.

1. The excitatory actions of phenylephrine (Phe) and acetylcholine (ACh) on the smooth muscle of rabbit portal vein were investigated and compared by using whole-cell and single channel configurations of the patch clamp technique, in combination with a modified concentration jump method. 2. At negative holding potentials with KCl (0.1 mM EGTA) electrodes, rapid applications of Phe (> 1 microM) and ACh (> 10 microM) both resulted in biphasic responses consisting of fast outward or inward currents and a long-lasting inward current with an increased noise level. 3. The slow inward current was still recorded when the cell was dialysed with caesium aspartate solution complemented with 10 mM EGTA, in order to eliminate contributions of calcium-dependent conductances (K+ and Cl- currents). Phe was more potent at activating the current than ACh. Ion replacement experiments revealed that both the Phe- and ACh-induced slow inward currents are cation-selective conductances (CS currents). 4. The I-V relationships of the Phe- or ACh-induced CS currents were similar both for the instantaneous peak and the steady state. The tail current analysis over a wide range of membrane potentials (-150 to +100 mV) showed that depolarizations to very positive potentials (> +50 mV) from near the resting membrane potential (-40 mV) can produce a several-fold increase in the steady-state activation of the CS currents, but the maximal activations were in most cases not observed even at +100 mV. 5. Externally applied Cd2+ produced a quick and reversible inhibition of both the Phe- and ACh-induced CS currents. This inhibition seemed almost voltage independent and the concentrations of half-inhibition were 100 and 129 microM for Phe and ACh, respectively. 6. Single channel activities were recorded in the presence of Phe or ACh using the outside-out membrane patches. The unitary conductances and reversal potentials of the Phe- and ACh-activated channels were 23 pS, +5.2 mV and 25 pS, +4.1 mV, respectively, and the open lifetimes evaluated for 50 microM Phe and 500 microM ACh were of similar order (the longer open times at -60 mV for Phe and ACh were 4.3 and 4.4 ms, respectively). In addition, the relative open probability (Po,rel) was no more than 0.2 in the voltage range of -100 to -30 mV for both 50 microM Phe and 500 microM ACh, suggesting low open probabilities of the Phe- and ACh-activated CS channels near the resting membrane potential.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

Defective calcium-dependent signal transduction in B lymphocytes of a certain common variable immunodeficiency.

Two different common variable immunodeficiency patients were studied. Patient 1 showed hypogammaglobulinemia in all major classes of gammaglobulins and slightly reduced percentages of circulating CD19+ cells, CD20+ cells and surface IgG-or IgA-bearing cells with a normal percentage of surface IgM-bearing cells. Patient 2 showed normal levels in IgM with IgG and IgA deficiencies and almost normal percentages of circulating CD19+ cells, CD20+ cells and surface IgM-, IgG- or IgA-bearing cells. The proliferative responses of peripheral blood mononuclear cells to B cell mitogen, Staphylococcus aureus Cowan I, were reduced in patient 1 but not in patient 2. The intracellular calcium concentrations in lymphoblastoid cell lines (LCLs) transformed by Epstein-Barr virus from patient 2 were increased after anti-mu stimulation. The concentrations were scarcely increased in LCLs from patient 1. These results suggest that B cells of patient 1 have a defective Ca(2+)-dependent signal transduction pathway, resulting in a failure of cell activation and cell proliferation. The defect in B cells of patient 2 may exist on immunoglobulin gene switching or expression rather than the Ca(2+)-dependent signal transduction pathway.

Agammaglobulinemia↗

Predominance of a distinct subtype of hairy cell leukemia in Japan.

Forty Japanese patients with hairy cell leukemia (HCL) were reviewed. Nine cases were diagnosed as typical HCL, and two cases had the features of HCL variant (prolymphocytic variant). The remaining 29 cases (72.5%) differed morphologically and hematologically from the other two groups in that they usually had a moderately high leukocyte count (average 27.9 x 10(3)/microliters), and abnormal cells showing a densely stained round nucleus and an inconspicuous nucleolus. Tartrate-resistant acid phosphatase reaction was weak, and their cells exhibited generally smooth or slightly irregular, cellular outlines in smears. The cells showed weak expression of surface immunoglobulin G (IgG) with kappa-chain predominance. CD25 antigen was not detected. Some of these findings resemble those of B-cell chronic lymphocytic leukemia, but the patients also had several important features of HCL. They had splenomegaly without significant lymphadenopathy. The abnormal cells were CD20+, CD11c+ and showed typical 'hairy morphology' under phase-contrast and scanning electron microscopy. Furthermore, spleen sections revealed diffuse infiltration by the abnormal cells in the red pulp. From these findings, we speculated that this group of patients constitute a distinct subtype of HCL which is commonly seen in Japan. We propose to term the disease as HCL Japanese variant.

Acid Phosphatase↗

[Multiple myeloma and adhesion molecules].

The physiological role of fibronectin (FN) on the human plasma cells were examined using three PC cell lines, FR4ds, OPM1 and OPM1ds. FR4ds was reactive with anti-VLA-alpha 4 and anti-alpha 5. In contrast, OPM1 and OPM1ds were not reactive with anti-VLA-alpha 5. FN induced spreading in FR4ds and OPM1ds. Albumin blocked these spreadings. FR4ds with mature plasma cell phenotype of alpha 4+ and alpha 5+ was more sensitive for FN than OPM1 and OPM1ds with immature phenotype of alpha 4+ and alpha 5-. Spreading cells proliferated more than floating cells. All these cell lines showed chemotaxis toward FN. alpha 5+ FR4ds was more sensitive for FN than OPM1 and OPM1ds with alpha 5- phenotype. These new abilities of PC of spreading and chemotaxis we found are summarized to be an affinity to organs. It is likely that alpha 4+ and alpha 5- PC with low affinity to organs are stored in peripheral blood as a result. We examined the chemotaxtic activity of myeloma cells in bone marrow and these in pleural effusions in a patient with multiple myeloma. These cells in pleural effusions showed more chemotaxic activity than these in bone marrow. FN induced growth, production of Ig, and motility of PC, which resulted in the augmentation of humoral immunity.

Bone Marrow Cells↗

Portal hypertensive gastropathy in patients with cirrhosis.

Portal hypertensive gastropathy is a recently recognized important complication of cirrhosis. In the present study, the clinical features, portohepatic hemodynamics, and hepatic function were investigated in a series of 47 patients with cirrhosis. Mild gastropathy was found in 15 patients (32%) and severe gastropathy in 17 patients (36%). The presence of gastropathy seemed to be independent of age, sex, cause of cirrhosis, or grade of gastroesophageal varices. However, severe gastropathy was associated with an increase in portal venous pressure gradient (vs. control, P less than 0.01; vs. mild gastropathy, P less than 0.01), an increase in hepatic sinusoidal resistance (vs. control, P less than 0.01; vs. mild gastropathy, NS), and a decrease in hepatic blood flow (vs. control, P less than 0.01; vs. mild gastropathy, NS). In addition, patients with severe gastropathy had impaired metabolic activity of the liver, which was assessed by intrinsic clearance of indocyanine green (vs. control, P less than 0.01; vs. mild gastropathy, NS). These observations may have important therapeutic implications in patients with cirrhosis and portal hypertensive gastropathy.

Aged↗

The Rolandic mu rhythm: a clinical study of the atypical group.

We studied 241 patients whose electroencephalograms (EEGs) showed 7-13 Hz arch shaped wave patterns (mu rhythm) that are known to appear in the Rolandic area. The patients were then classified into two groups depending on the conditions of appearance of the mu rhythm. Group I (typical group) consisted of 171 cases. In this group, the presence of the wave patterns was not affected by the opening of the eyes, and it was blocked by spontaneous movements, or when sensorimotor stimulation was applied. The characteristic symptoms for this group were observed in patients diagnosed as having well-controlled epilepsy, psychiatric disorders, collagen diseases, etc. In Group I, the peak lay between the ages 6 through 15. Group II (atypical group) consisted of 70 cases. In contrast to Group I, the presence of the wave patterns in this group was reinforced by drowsiness, photic stimulation and hyperventilation. The characteristic symptoms for this group were observed in patients diagnosed as having intractable epilepsy or organic brain disorders. In Group II the peak lay between ages 11 through 15. However, in Group II the cases were almost equally distributed among the various age groups. Paroxysmal abnormal EEG patterns were found to be jointly present with more frequency in the Group II sample of epileptic patients than the Group I sample. Therefore, when the mu rhythm associated with conditions indicating Group II type patients is observed, care must be exercised in the observation of further progression of the illness, and in searching for the possibility of organic brain disorders.

Adolescent↗

Frontal spindle activity that appears in conjunction with nontraumatic diffuse encephalopathy.

This peculiar 11-14 Hz spindle activity appears predominantly in the frontal area, and was observed in eight patients with impaired consciousness caused by nontraumatic diffuse encephalopathy. Characteristic of this frontal spindle activity is its transience and accordance with changes in the arousal level of the patient. When the degree of impaired consciousness in the patient was minimal and clinically not very apparent, this spindle activity appeared during light drowsiness. In lethargic patients, it was observed when the patient's level of consciousness rose (e.g. immediately after opening and closing the eyes). These frontal spindles disappeared at the onset of Stage 2 sleep, when normal physiologic spindle waves that are dominant in the vertex area appeared. A paroxysmal discharge was sometimes recorded in association with the frontal spindle activity and it disappeared at about the same time as these spindles. The prognosis was satisfactory for all patients in whom frontal spindle activity was observed; its correlation to spindle coma is also studied.

Adolescent↗