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Biomedical subjects

K Iida

Publications and source records attributed to K Iida.

At least 361 records · Page 20Linked to original sources

Intraoperative radiotherapy for advanced carcinoma of the pancreas.

A detailed retrospective analysis of the efficacy of intraoperative radiotherapy (IOR) in advanced carcinoma of the pancreas is presented. During a 10-year period from 1973 through 1982, 70 patients with advanced carcinoma of the pancreas were treated by multimodal methods, separate or combined therapy of surgery, IOR, and chemotherapy in two different institutions. Among these, 33 patients underwent IOR, mostly combined with additive surgery. A single dose of 20.1 to 40.0 Gy with 8 to 25 meV electrons was delivered through radiation cones ranging from 6 to 10 cm in diameter. Excellent relief was noticed in 50% of the patients who had complained of pain. Among Stage IV patients, a significant difference of survival rate was observed between IOR and control groups (P less than 0.05); the mean survival time of the IOR group was 4.6 +/- 2.6 (SD) and that of the control group 2.5 +/- 1.4 (SD) months. Intraoperative radiotherapy proved to be effective in prolonging the survival of patients with advanced stage of the lesion.

Adult↗

Deficiency in C3b receptors on neutrophils of patients with chronic granulomatous disease and hyperimmunoglobulin-E recurrent infection (Job's) syndrome.

C3b receptor (CR1) expression by neutrophils (PMNs) and erythrocytes (Es) from patients with chronic granulomatous disease (CGD) or with hyper-IgE, frequent infection (Job's) syndrome was compared with that of control subjects. The control subjects consisted of one group of patients with infections and a second group of normal, healthy individuals. Three quantitative assays were used: rosette formation with C3b-coated cellular intermediates (EAC43b), binding of radiolabeled monoclonal anti-CR1 ([125I]anti-CR1) to PMN surfaces, and binding of the antibody to nonidet P-40 (NP-40) extracts of PMNs and Es in an immunoradiometric assay. Rosette formation by the PMNs of five male CGD patients was about 50% of that of paired normal control subjects, whereas the rosette formation of three female CGD patients was similar to that of the control subjects. Surface binding of [125I]anti-CR1 to PMNs of 10 CGD patients was about half that of the normal subjects (mean percent binding was 2.33% for the CGD patients vs. 3.86% for the normal subjects, giving a difference of -1.53 +/- 0.22%, P less than 0.001 by the paired-sample t test). The degree of PMN binding was similarly low for both the male and the female CGD patients. Conversely, the binding of anti-CR1 to the PMNs of 11 infected control patients appeared to be similar to that of the normal subjects (4.51% for the patient vs. 4.21% for the paired normal subjects). The infected control group originally included four Job's syndrome patients, and when this subgroup was analyzed separately, their PMNs were shown to bind significantly less anti-CR1 than did the PMNs of the normal subjects (P less than 0.01 by the paired-sample t test). In contrast, the other infected control patients showed higher-than-normal levels of anti-CR1 binding (P less than 0.05). When compared to that of the normal subjects, the total CR1 quantitated in PMN extracts was also lower than normal in CGD patients (P less than 0.01 and in the PMN extracts of eight Job's syndrome patients tested (P less than 0.01). The PMNs of the other infected control subjects were not significantly different from those of the normal subjects in total CR1 expression. Extracts of Es from Job's syndrome patients also had fewer than normal CR1 (P less than 0.02). On the other hand, CR1 levels in E extracts from the CGD patients and the other control patients were similar to those in the normal control subjects. Quantitations of C3, C4, and factor B were normal in CGD.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigen-Antibody Complex↗

Occurrence of caldesmon (a calmodulin-binding protein) in cultured cells: comparison of normal and transformed cells.

Caldesmon is a calmodulin-binding and F-actin-binding protein originally purified from chicken gizzard smooth muscle. This protein binds to F-actin filaments in a Ca2+- and calmodulin-dependent "flip-flop" fashion, thereby regulating the function of actin filaments. Here we report that various lines of cultured cells contain a Mr 77,000 protein that specifically reacts with the affinity-purified caldesmon antibody raised against chicken gizzard caldesmon . Among the fibroblast proteins that had been pulse-labeled with [35S]methionine, the Mr 77,000 protein was the only protein band detected on the NaDodSO4 gel that reacted with the anticaldesmon . The subcellular distribution of the Mr 77,000 protein was investigated by the indirect immunofluorescence technique using the anticaldesmon . In all fibroblast cell lines examined, the immunofluorescence localized along the cellular stress fibers and in leading edges of the cell. In Rous sarcoma virus-transformed cells (S7-1), however, the distribution of the fluorescence changed to a diffuse and blurred appearance. These staining patterns of anticaldesmon obtained with the normal and transformed cells coincided with those of antiactin in the corresponding states, strongly suggesting the functional linkage between the Mr 77,000 protein and actin filaments. We propose to refer to this Mr 77,000 protein as caldesmon 77. The cellular level of caldesmon 77 in transformed S7-1 cells decreased to about one-third of that in their normal counterparts (cell line no. 7). Essentially the same result was obtained with normal rat kidney cells infected with the temperature-sensitive transformation mutant Schmidt-Ruppin strain of Rous sarcoma virus (68 N2 clone). The cellular level of caldesmon 77 observed at a permissive temperature (35 degrees C) was about one-third of that at a nonpermissive temperature (38.5 degrees C). These changes of caldesmon 77 in transformed cells may correlate with the loss of Ca2+ regulation in the transformed state.

Animals↗

Mechanisms of adverse effect of air-oxidized soy bean oil-feeding in rats.

In order to clarify the mechanism of the adverse effects of air-oxidized oil feeding, the effects of dietary soy bean oil on body weight gain, food consumption, fecal consistency and gastrointestinal functions were investigated in rats. Feeding of oxidized soy bean oil with a peroxide value above 350 produced significant reductions in body weight gain, food consumption and intestinal sucrase activity, and severe diarrhea. These adverse effects were prevented with the concurrent feeding of Gobo dietary fiber and were rapidly eliminated within a day after switching to the diet containing the unoxidized soy bean oil. Furthermore, the remarkable release of sucrase from the small intestine was observed on perfusion of the jejunum with Ringer's bicarbonate solution containing the oxidized soy bean oil at the 1% level. These findings suggest that the adverse effects occurring after air-oxidized oil feeding are due to a disturbance of gastrointestinal functions, and raise the possibility that the primary cause might be solubilization or exfoliation of the brush border membrane.

Air↗

Functional significance of coronary collateral vessels during exercise evaluated by radionuclide angiocardiography: the importance of supplying arteries.

To investigate the function of coronary collateral vessels, especially from view point of supplying arteries, radionuclide angiocardiography was performed before and during a symptom-limited ergometer exercise in 54 patients with effort angina. In single vessel disease, during exercise, left ventricular ejection fraction (EF) (%) increased in the cases with coronary collateral vessels (supplied from patent arteries) (72 +/- 7----77 +/- 8, p less than 0.025), but decreased in those without (66 +/- 10----61 +/- 10, P less than 0.001). In multivessel disease, EF decreased during exercise even in those with collaterals (supplied from stenosed arteries) (67 +/- 10----59 +/- 8, p less than 0.001). It is concluded that angiographic appearance of the coronary arteries supplying collateral vessels is a major predictive factor of the function of coronary collateral vessels and of left ventricle during exercise.

Adult↗

[Pathophysiology of asymmetric septal hypertrophy with special reference to the response to isoproterenol administration].

To investigate the pathophysiological significance of asymmetric septal hypertrophy (ASH), echocardiograms were recorded in 25 patients with hypertension (HT) (12 with ASH, 13 with symmetric hypertrophy (SH), 19 patients with hypertrophic non-obstructive cardiomyopathy (HNCM) (eight with ASH, 11 with SH), and 12 patients with hypertrophic obstructive cardiomyopathy (10 with ASH and two with SH). In eight patients with ASH, 12 patients with SH and eight normal controls, echocardiograms were also recorded during intravenous infusion of 0.02 mu/kg/min of isoproterenol. There were no significant differences in end-diastolic dimension (EDD), end-systolic dimension (ESD), percent fractional shortening (%FS), interventricular septal excursion (IVSE) and posterior wall excursion (PWE) between patients with ASH and patients with SH. Among patients with ASH, interventricular septal thickness (IVST) and its ratio to posterior wall thickness (IVST/PWT) were significantly larger in HOCM than in others. Before isoproterenol infusion, there was no significant difference in the normalized peak rate of change of left ventricular dimension during systole (pVs) between ASH and SH, and between ASH and NC. However, 5 min after isoproterenol infusion, pVs was significantly greater in ASH (7.0 +/- 2.4/sec) than in SH (4.9 +/- 1.3/sec) and in NC (4.5 +/- 1.1/sec) (p less than 0.05 and p less than 0.05, respectively). This study suggests that ASH is related to hyperfunction of the catecholamine-beta receptor system.

Adult↗

Identification of the membrane receptor for the complement fragment C3d by means of a monoclonal antibody.

The B2 antigen characterized by means of a monoclonal antibody (14) is a 140,000 Mr protein expressed only in certain stages of the differentiation of lymphocytes of the B lineage. Here we examine the relationship between B2 and the membrane complement receptor type 2 (CR2) for the complement fragment C3d (11, 12), which is also associated only with B cells. Both phenotypic markers are distributed in a similar manner among B cell malignancies and, as shown here, among established cell lines. A polypeptide with binding affinity for C3d was isolated from the membrane of B2-positive cells, i.e., tonsil lymphocytes and Raji cells. We found that this C3d-binding protein not only had the same Mr and isoelectric point (pI) as the B2 antigen, but that it was recognized by the monoclonal antibody to B2. However, anti-B2 does not mask the ligand-binding site of CR2 since it does not prevent the interaction of the purified 140,000 Mr polypeptide with immobilized C3d. Rosette formation between tonsil lymphocytes and erythrocyte intermediates bearing C3d was specifically inhibited by anti-B2. In the case of Raji cells, rosette formation was strongly inhibited only when the lymphocytes were sequentially treated with anti-B2 and with a polyclonal antibody against mouse Ig. In short, B2 and CR2 have a similar distribution among normal and malignant cells, have the same Mr and pI under denaturing conditions, and react with a single monoclonal antibody. We conclude that B2 is identical to CR2.

Animals↗

Structural heterogeneity of the C3b/C4b receptor (Cr 1) on human peripheral blood cells.

In these studies CR 1 polymorphism previously demonstrated on erythrocytes (E) was also found on CR 1-bearing peripheral blood leukocytes including polymorphonuclear (PMN), eosinophils, monocytes, and B lymphocytes. However several cell-specific differences in CR1 were found: (a) an approximately 5,000-dalton increase in CR 1 on PMN and eosinophils, (b) unequal band intensity among heterozygotes suggests that there is preferential expression of 220,000- or 225,000-dalton receptors on leukocytes compared to E, and (c) "minor" bands, approximately 15,000 daltons larger than the major receptor molecule, were found on E but not on leukocytes. These observations constitute a unique example of heterogeneity of an integral membrane receptor.

B-Lymphocytes↗

Mutants of Escherichia coli defective in penicillin-insensitive murein DD-endopeptidase.

Two mutants of Escherichia coli that are deficient in the penicillin-insensitive DD-endopeptidase have been isolated. The strain JE10874 (mepA) has about 10%-20% of the residual activity and another strain, JE10368 (mepB) has 40%-50% of the activity found in the wild-type, parental strain, PA3092. The penicillin-insensitive endopeptidase is a periplasmic enzyme. Genetic mapping studies show that the mutation mepA is located close to aroC (50 min) and the other mutation, mepB, is very close to malE (91 min) on the chromosome. These mutants grow normally under a wide range of growth conditions; other phenotypic properties of the mutants are very similar to those of the parent strain. A double mutant (mepA mepB), and a triple mutant (mepA mepB dacB), deficient in both penicillin-insensitive and penicillin-sensitive endopeptidases, were constructed. Again, these mutants grew normally. We conclude that either the very low level of residual enzyme activity in the mutants is enough for their survival or that the penicillin-insensitive endopeptidase is not essential for survival under laboratory conditions.

Chromosome Mapping↗

Monoclonal antibodies to human complement receptor (CR1) detect defects in glomerular diseases.

The complement receptor for C3b of the epithelial cells of human glomeruli is structurally and functionally very similar or identical to CR1, the complement receptor for C3b and C4b present on the membrane of red cells and leukocytes. Four monoclonal antibodies directed against separate epitopes of CR1 react with an antigen in the glomeruli, which appears to be present on the epithelial podocytes. Moreover, the monoclonal antibodies very effectively inhibit the binding of C3b-bearing red cells to the glomeruli. The pattern of immunofluorescence of the receptor was normal or slightly altered in patients with minimal change disease, mesangial proliferative glomerulonephritis (GN), or idiopathic membranous GN. Glomeruli with endocapillary proliferation showed some attenuation of staining. Glomeruli in which the capillary tuft architecture was altered, or of patients with systemic lupus erythematosus, or of patients with diffuse diabetic nephropathy tended to have few foci or no staining for the receptor. No correlation was found between the intensities of staining of the C3b receptor and of C3 antigen deposited in the glomeruli.

Amyloidosis↗

Identification of the C3bi receptor of human monocytes and macrophages by using monoclonal antibodies.

We have obtained four monoclonal antibodies, IB4, OKM1, OKM9, and OKM10, all directed against the C3bi receptor of human monocytes and macrophages (M phi). Two criteria were used to determine the specificity of these antibodies. First, culture surfaces coated with the antireceptor antibodies caused specific down modulation of C3bi receptor activity on M phi adherent to these substrates. Second, receptor protein purified by using IB4 or OKM1 retained the ability to bind selectively to C3bi-coated erythrocytes. Each of the antibodies recognizes a distinct epitope on the C3bi receptor; they do not compete with one another for binding to monocytes. Further, when immobilized on a solid support, each of the antibodies binds a molecule from M phi lysates that can simultaneously bind one of the other monoclonal anti-C3bi receptor antibodies. OKM10 binds and masks the ligand-binding site of the C3bi receptor, while IB4, OKM1, and OKM9 bind to sites remote from the C3bi binding site. All four antibodies immunoprecipitated polypeptides of Mr 185,000 and 105,000 from 125I-surface-labeled M phi. IB4 also precipitates polypeptides of Mr 185,000, 153,000, and 105,000. We conclude that the C3bi receptor of human M phi is a complex composed of two polypeptides, Mr 185,000 and 105,000. We have identified monoclonal antibodies reacting with four distinct antigenic determinants of this complex. The determinant recognized by antibody OKM10 is at or near the ligand-binding site of the receptor. The determinant recognized by antibody IB4 is shared by at least two other leukocyte surface proteins.

Animals↗

Polymorphism of human erythrocyte C3b/C4b receptor.

The human erythrocyte receptor for the major activation fragments of the third and fourth components of complement (HuE-C3bR) was isolated from individual donors. Erythrocytes were surface labeled with 125I and solubilized in Nonidet P-40.HuE-C3bR was purified by using C3-Sepharose affinity chromatography and analyzed by autoradiography of NaDodSO4/polyacrylamide gels. Three distinct receptor patterns were demonstrated. Type a had a single major band with Mr of 190,000, type b had a single major band with Mr of 220,000, and type c had two major bands of Mr 190,000 and 220,000. In all three types, a minor band accounting for less than 25% of the total radioactivity was usually observed at a Mr 15,000 greater than that of each major band. Identical autoradiographic patterns were obtained by affinity chromatography using methylamine-inactivated C4-Sepharose or by immunoprecipitation of solubilized membranes with a monoclonal antibody against HuE-C3bR. All three types were distinct after reduction and alkylation, although the apparent Mr uniformly increased by approximately equal to 30,000. Characterization of HuE-C3bR types in 33 unrelated individuals demonstrated that 23 had type a, 1 had type b, and 9 had type c. Family studies provide evidence for transmission by two codominant alleles. Thus, in the normal population two alleles appear to control expression of HuE-C3bR phenotypes and account for the polymorphism of this integral membrane glycoprotein.

Complement C3↗

Sudden cardiac death at exertion.

In order to investigate sudden cardiac death at exertion (sports, and light work in daily life), 226 cases of sudden death during sports and 1,729 autopsy cases of sudden death were studied, and exercise tests were performed on 138 patients with various cardiac diseases. Among sports, marathon or jogging caused sudden death most frequently (52.7%). It occurred often immediately after goal (41.3%) or before goal (28.0%), but cases with a history of heart disease died at the beginning of the race. Severe heat, overwork and other factors may precipitate the sudden death. In autopsy cases of sudden cardiac death which occurred at exertion, coronary arteriosclerosis (C) was found in 67.0%, cardiac hypertrophy of unknown etiology (H) in 7.8% and valvular heart diseases (V) in 7.1%. Sudden death in patients with C or H were more frequent at exertion than at rest. Patients with C were older and died at light work. Those with H of a high degree also died at light work, but the younger ones with a mild H died at sports activity. At exercise test, in patients with arrhythmia or hypertrophic cardiomyopathy, abnormalities may occur after exercise. Sudden death at exertion may depend on the predisposing heart disease. Care should be taken especially at the end of the race.

Adolescent↗

Functional properties of membrane-associated complement receptor CR1.

It was previously shown that membrane receptors for C3b (CR1) purified from human erythrocytes were powerful inhibitors of the complement cascade and that they encompass the regulatory functions of the serum proteins beta 1H (H) and C4-binding protein (C4bp). In the present report we study the functional properties of membrane-associated CR1. When tonsil lymphocytes, which contain between 30 and 60% of CR1-bearing B cells, are incubated with the red cell complement intermediate EAC14oxy2lim or EAC14oxy23lim, they inhibit both C42 and C423 in a dose-dependent manner. These effects are mediated by membrane-associated molecules. Indeed, mild trypsinization of the lymphocytes abolishes their activity, and formaldehyde-fixed cells are as effective as viable cells. The inhibitory effects are in part mediated by CR1. The lymphocyte activities are reversed about 60% if monoclonal antibodies to CR1 or fluid phase C3b are present in the incubation medium. Moreover, upon addition of C3b-inactivator (l), lymphocytes release C3c fragments from EAC14oxy23b. The release of C3c was also abolished by antibodies to CR1. These results support the idea that CR1, as well as other molecules from the lymphocyte membrane, can function as inhibitor(s) of complement activation in their vicinity.

Animals↗