[Analysis of anti-HIV antibody and the production of monoclonal antibodies].
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Biomedical subjects
K Sagawa
Publications and source records attributed to K Sagawa.
Characterization of three monoclonal antibodies (VAK3-5) that identify p24, core protein of human immunodeficiency virus, and its precursors.
VAK3, VAK4 and VAK5 monoclonal antibodies (mAbs) were raised by using disrupted purified human immunodeficiency virus (HIV) as an antigen. These mAbs exclusively reacted with an HIV-infected cell line, H9/HIV, and did not react with human T cell lymphotropic virus (HTLV)-I or -II infected cell lines. Strip radioimmunoassay based on the Western blotting technique revealed that these mAbs recognize a single band that corresponds to a 24-kd (p24) core protein of HIV when disrupted viruses were used as antigens. When cell lysates of H9/HIV were used as antigens, these mAbs gave two bands with molecular weights of 40 kd (p40) and 57 kd (p57) in addition to p24. VAK5-conjugated Sepharose 4B beads precipitated non-glycosylated proteins, p24, p40 and p57 from [L-35S]methionine-labeled H9/HIV. P57 and p40 appear to be a precursor and an intermediate precursor of p24, respectively. Purified IgG of VAK3 and VAK4, and the serum from an individual infected with HIV inhibited the binding of VAK5 mAb to HIV. These findings suggest that p24 of HIV contains structure(s) with strong antigenicity.
Animals↗
[Human leukocyte differentiation antigens and the International CD (cluster of differentiation) classification].
Explore the source record for details and available documents.
Antigens, Differentiation↗
Phenotyping of malignant hematopoietic cells. Analysis of 1200 cases of leukemia-lymphoma.
1255 cases of leukemia-lymphoma were tested between 1972 and 1984 by multiple marker analysis. Routine leukemia phenotyping was performed using standard morphological and cytochemical techniques in combination with clinical and histo-pathological information; the main emphasis was put on immunological surface marker analysis using erythrocyte rosette assays, TdT and a large panel of poly- and monoclonal antibody tests. The 1255 cases were divided into these major types and subtypes: 349 cases of ALL and related immature T- and Burkitt-lymphomas (cALL, pre B-ALL, B-ALL and Burkitt-lymphomas, T-ALL and immature, mostly leukemic T-lymphomas, Null-ALL), 454 cases of mature T- and B-cell malignancies (T-CLL, mycosis fungoides, Sezary-syndrome, T-lymphomas, B-CLL, hairy cell leukemia, multiple myeloma, B-lymphomas), 263 cases of acute myeloid leukemias (AML, AMMoL/AMoL), 182 cases of chronic myeloid leukemias (CML in chronic phase, CMoL, CML in blast crisis), 6 cases of erythroleukemia and 1 case of megakaryoblastic leukemia. A simplified classification scheme which has been used in our laboratories is presented. Phenotyping is of diagnostic, prognostic and therapeutic relevance, most evidently for patients with ALL. Routine leukemia phenotyping should be performed with highly standardized techniques and reagents and by combining information from several fields in the multiple marker analysis. New areas of leukemia research might become very useful for the routine procedure of phenotyping.
Adult↗
Reactivity pattern of 'myeloid monoclonal antibodies' with emphasis on MCS-2.
The reactivity pattern of the murine monoclonal antibody (MoAb) MCS-2 was tested on a panel of 724 cases of leukemia-lymphoma. MCS-2 was positive in 178/185 (96%) cases of AML (FAB M1-3), 10/10 cases of AMMol/AMoL (FAB M4/5), 42/45 (93%) cases of CML, 1/1 case of CMoL, 37/38 (97%) cases of CML-myeloid blast crisis, 0/9 cases of CML-lymphoid blast crisis. No positive staining was seen in 238 cases of T-CLL, mycosis fungoides, Sèzary-syndrome, B-CLL, hairy cell leukemia, multiple myeloma and T- and B-lymphoma nor in 32 cases of B-ALL, Burkitt-lymphoma, Null-ALL and immature T-lymphoma. A positive expression was found in 8/110 cases of cALL, 1/6 cases of pre B-ALL and 1/35 cases of T-ALL. Fifteen other MoAbs (MCS-1, OKM1, My-1, Leu-M1, Leu-M3, CA-2-38, MY4, MY7, MY8, MY9, VIM-D2, VIM-D5, Mol, Mo2, 63D3) which are associated with the myelomonocytic cell lineages were tested by indirect immunofluorescence on 60 or more patients (62-149 cases). A wide variability in the frequency of positivity was seen for the panel of cases studied and for the blast cell populations per individual samples: 21-96% of the AML cases (FAB M1-3) and 31-100% of the AMMoL/AMoL cases (FAB M4/5) were positive for the various MoAbs. None of the analysed MoAbs stained only myelocytic or only monocytic leukemias, but a certain degree of preference for the monocytic variants was noted for Leu-M3, CA-2-38, MY4, VIM-D2, Mo2 and 63D3. The detection of MCS-2 on immature ALL blast cells might indicate a coexpression of lymphoid and myeloid markers on very immature cells, or an abnormal gene expression by malignant cells, or the identification of a so far undetected subclass of acute leukemias.
Adult↗
Influence of pacing site on canine left ventricular force-interval relationship.
We tested the hypothesis that while absolute extrasystolic (ES) and postextrasystolic (PES) dP/dtmax would be influenced by pacing site, if these values were normalized by the steady-state dP/dtmax obtained with the same pacing site, they would be independent of pacing site. We employed an isovolumetrically contracting isolated heart preparation with a balloon placed in the left ventricle. Pacing electrodes were placed on the atrium and four different epicardial ventricular sites. While pacing from each site separately, a steady mechanical state was established at a constant rate, and the interval between beats was then perturbed. The same pacing sequence was used while pacing from each of the five sites. On each ES and PES beat, dP/dtmax was expressed as a percentage of the steady-state dP/dtmax. The normalized responses measured with each ventricular pacing site (DPventr) were plotted as a function of the normalized responses obtained with atrial pacing (DPatr). On average, DPventr = 1.02 DPatr - 3.2% (n = 6, with r2 = 0.989), indicating that pacing site did not significantly influence the "normalized" force-interval relationship. Thus the basic information retrievable from measurements of the ventricular force-interval relationship is independent of the site from which the heart is paced.
Animals↗
Influence of pacing site on canine left ventricular contraction.
We investigated the influence of pacing site on several aspects of left ventricular (LV) performance to test the hypothesis that "effective ventricular muscle mass" is reduced with direct ventricular pacing. All studies were performed on isolated supported canine hearts that were constrained to contract isovolumically. To determine the influence of pacing site on magnitude and time course of isovolumic LV pressure (P) generation, LVP waves were recorded in eight isolated hearts paced at 130 beats/min. Pacing was epicardially from atrium, LV apex, LV free wall, right ventricular free wall (RVF), and endocardially from right ventricular endocardium. In a given heart, peak LVP was greatest with atrial pacing and smallest with RVF pacing, the difference being on average 26 +/- 10% (mean +/- SD) of the former pressure. The other pacing sites produced intermediate peak LVPs. When instantaneous LVP waves, obtained while pacing from each of the five sites, were normalized by their respective amplitudes, they were virtually superimposable up to the time of peak pressure and only slightly different during the remainder of the cardiac cycle. With changes in pacing site there was a linear negative correlation (r = 0.971) between changes in peak pressure and changes in duration of the QRS complex of a bipolar epicardial electrogram with an average slope of -0.51 mmHg/ms. Compared with atrial pacing, the slope of the end-systolic pressure-volume relation, Ees, was decreased with ventricular pacing, but Vo, the volume axis intercept, was relatively constant.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Time sequential prediction of ventricular-vascular interactions.
A new analytical method (sequential convolution) for describing ventricular-vascular interactions was used to predict instantaneous pressure and flow in four isolated canine left ventricles ejecting into a computer-simulated arterial system. Ventricular pumping ability was described by a load-independent elastance, [E*(t)] combined with a ventricular internal resistance. "Arterial" properties were characterized using a time-based impulse response function that is derived from impedance measurements. Sequential convolution was then used to couple these independent descriptions of ventricular and vascular properties. Predicted pressure-volume trajectories, as well as instantaneous pressures and flows, closely matched the experimental data. Stroke volume, peak pressure, and peak flow were typically within 5% of measured values. This method provides a powerful analytical technique for examining ventricular-vascular interactions and has potential application in evaluating the ventricular-loading effects of more complex in vivo vascular properties.
Animals↗
Ventricular efficiency predicted by an analytical model.
Based on the recent data from the literature, we derived analytic expressions for ventricular stroke work (SW), ventricular O2 consumption, and the ratio of the former to the latter, defined as ventricular efficiency, in terms of ventricular contractile properties and arterial afterloading properties. The ventricular properties were quantified by Ees and V0, the slope and volume axis intercept, respectively, of the linear end-systolic pressure-volume relationship. Ventricular afterload was represented by the effective arterial elastance (Ea), a parameter that is dependent on aortic input impedance parameters. O2 consumption was assessed by estimating ventricular pressure-volume area, which has been shown to be linearly related to O2 consumption. Model analysis indicated that SW is maximum when Ea = Ees, the afterload that results in the greatest efficiency is always less than that which provides the maximum SW, the SW and efficiency of a weak heart are more sensitive to changes in afterload than in a strong heart, and there is a sigmoidal relation between ventricular efficiency and end-diastolic volume that reaches its maximum at volumes outside the upper limit of the physiological range. Further analysis of the model indicated that under physiological conditions ventricular and arterial properties may be adjusted more toward optimization of efficiency than SW.
Forecasting↗
Determination of left ventricular end-systolic pressure-volume relationships by the conductance (volume) catheter technique.
Using a multielectrode conductance catheter to estimate continuous left ventricular volume we determined the end-systolic pressure-volume relationship (ESPVR) in situ in open-chest anesthetized dogs. Dogs (n = 8) were studied in the control state and after pharmacologic sympathectomy (hexamethonium) and surgical vagotomy both before and after the administration of dobutamine. ESPVR was measured during brief (5 to 6 sec) preload reduction by balloon occlusion of the inferior vena cava (IVCBO). The relationship was highly reproducible. The slope (Ecs) and volume intercept (Vo) (mean +/- SD) in the control series were 5.8 +/- 3.6 mm Hg/ml and 6.5 +/- 12.5 ml, respectively. Upon release of the IVCBO (preload recovery), Ecs was 7.7 +/- 3.6 mm Hg/ml and Vo was 12.4 +/- 9.6 ml (p less than .01). Autonomic blockade produced a 50% reduction in Ecs and a concomitant decrease in Vo (p less than .01), and eliminated the difference between ESPVR generated by preload reduction (IVCBO) and preload recovery (IVCBO release). Subsequent dobutamine infusion increased Ecs to 6.1 +/- 3.5 mm Hg/ml and Vo to 4.1 +/- 6.9 ml, consistent with reported changes of the ESPVR with positive inotropic intervention. A small artifact of right ventricular filling was observed in the left ventricular volume catheter signal, but this did not appreciably alter the ESPVR. These results demonstrate the feasibility of the determination of ESPVR in situ by the conductance catheter and brief IVCBO and underline the importance of the use of rapid load changes to minimize reflex activation during the measurements.
Animals↗
Spectral luminous efficiency functions in the mesopic range.
Spectral luminous efficiency functions for mesopic vision were measured extensively to establish a basic data set for the mesopic photometry system. These functions were obtained by the direct brightness matching for a 10 degrees field at nine retinal illuminance levels from 100 to 0.01 Td in 0.5-log-unit steps. Data for 12 subjects were collected. In the mesopic range, the spectral luminous efficiency function, averaged over 12 subjects, gradually changes form with retinal illuminance. This suggests that the mesopic function should be established for all the levels in that range. An attempt was made to find an empirical formula that expresses the mesopic function as a simple combination of the photopic and the scotopic brightness functions.
Humans↗
Establishment of a hairy cell leukemia cell line carrying Tac antigen and phagocytic activity with B-cell characteristics.
A hairy cell leukemia cell line designated "Hair-M" was established in a suspension culture derived from the peripheral blood of an 86-year-old Japanese male with a diagnosis of hairy cell leukemia. The Hair-M cells were identified as having prominent hair-like cytoplasmic projections by examination with phase-contrast and scanning electron microscopy. These cells displayed ruffled membranes and stublike microvilli similar to those observed on the surfaces of cells in the peripheral blood of the patient. Immunologic and cytochemical studies on the Hair-M cells confirmed derivation from the clone of the patient's leukemia cells. Although the cultured Hair-M cells had definite B-cell characteristics, such as IgG kappa-chains on the surface and in cytoplasm, they also demonstrated Tac antigen, which is usually expressed on activated T-cells, and myelomonocyte antigens determined by OKM-1 and MCS-1 monoclonal antibodies. Other cell surface markers, including E(-), IgGFc(-), IgMFc(-), C3R(+), Ia-like antigen(+), OKT9(+), OKT10(+), and terminal deoxynucleotidyl transferase(-), were detected; no Epstein-Barr virus-determined nuclear antigen was detected. The karyotype of the Hair-M cells was determined to be 46XY with -11, -14, and two marker chromosomes. The Hair-M cells also had phagocytic activity to rabbit anti-human IgG serum-coated polyacrylamide gel particles.
Aged↗
[Preparation of monoclonal antibodies to HTLV-III and their application].
Explore the source record for details and available documents.
Antibodies, Monoclonal↗
[Nursing of terminal patients and interactions with their families].
Explore the source record for details and available documents.
Humans↗
Clinical features of OKT4+/OKT8+ adult T-cell leukemia.
Adult T-cell leukemia (ATL) has a range of clinical characteristics. Phenotypically the leukemic cells usually express the helper/inducer associated antigen OKT4 with lack of OKT8. We have observed three patients with acute ATL cytologically indistinguishable from OKT4+/OKT8- ATL but whose neoplastic cells had the unusual phenotype, OKT3+, OKT4+, OKT6-, OKT8+ OKT9+/-, OKT11+, Tac+/-, TdT-. All patients had abnormal karyotypes and antibodies against anti-ATL associated antigens as well as proviral DNA of human T-cell leukemia virus in the leukemic cells. The clinical course was complicated by skin eruptions, hypercalcemia, pulmonary infection and disseminated intravascular coagulopathy. All died of complications shortly after diagnosis. The clinical features of these patients were similar to those of OKT4+/OKT8- ATL. However, their acute course suggests that co-expression surface antigens OKT4 and OKT8 may be a sign of aggressive nature of the disease with poor prognosis.
Aged↗
Stroke volume effect of changing arterial input impedance over selected frequency ranges.
We investigated the effect of changing arterial input impedance over three selected frequency ranges on stroke volume (SV) in nine isolated canine left ventricles. The input impedance was simulated with a three-element Windkessel model (i.e., resistance, characteristic impedance, and compliance) and was imposed on the ventricles with a servo-controlled loading system. Under a constant end-diastolic volume [33.1 +/- 1.5 (SE) ml], we changed the modulus of the afterloaded impedance over a low frequency range (below 0.13 Hz) by changing the resistance, over a transitional frequency range (in which the impedance modulus decreases from total resistance to characteristic impedance) by changing the compliance, and over a high frequency range (above 2.0 Hz) by changing the characteristic impedance. Each of the impedance components was changed from control to 50 and 200% of control. SV sensitively decreased from 16.1 +/- 0.7 to 7.4 +/- 0.5 ml in response to the increase in the low-frequency impedance modulus. SV was relatively insensitive, however, to the same percent increase in the impedance modulus over the transitional frequency range (from 11.2 +/- 0.6 to 12.3 +/- 0.7 ml) and over the high frequency range (from 11.9 +/- 0.6 to 11.6 +/- 0.7 ml). The average relative sensitivities of SV to the increase and decrease in impedance moduli in these frequency ranges were 1.2:0.12:0.04. We conclude that the modulus of impedance in the low frequency range is, by far, a more important determinant of SV than those in the transitional and high frequency ranges.
Animals↗
Hypotension 1.5 min after 10% hemorrhage permits evaluation of rabbit's baroreflex.
In seven chronically instrumented rabbits, we studied the influence of the vasopressin system on the evaluation of acute reflex compensation of arterial pressure for a mild hemorrhage. Rabbits were bled 10% of estimated blood volume in 1 min. The hemorrhage was repeated before and after administration of a vasopressin antagonist [d(CH2)5Tyr(Me)arginine vasopressin, 10 micrograms/kg] and in the conscious and anesthetized (pentobarbital sodium 20 mg/kg) state. The efficacy of the vasopressin antagonist was preliminarily tested in each rabbit by confirming its antagonism against the hemodynamic effects of infused vasopressin (50 ng X min-1 X kg-1). Mean arterial pressure (MAP), heart rate (HR), mean aortic flow (MAF), and total peripheral resistance (TPR) were measured before and at 1.5 min after completion of hemorrhage. The hemorrhage caused statistically significant decrease in MAP (84 +/- 6 to 78 +/- 6 mmHg) and MAF (195 +/- 28 to 158 +/- 26 ml X kg-1 X min-1) and increase in TRP (0.44 +/- 0.05 to 0.51 +/- 0.07 mmHg X kg X min X ml-1) and HR (271 +/- 21 to 284 +/- 22 beat/min). However, there was no statistically significant interaction in any variables between vasopressin and hemorrhage, i.e., whether vasopressin was blocked or intact did not affect the fall in MAP by hemorrhage. We conclude that in the rabbit vasopressin's role in the acute compensation of arterial pressure for a quick 10% hemorrhage is small enough to permit accurate estimation of the arterial baroreflex gain from the depressor responses to mild hemorrhage with and without the reflex function.
Animals↗
Alternating contractility in pulsus alternans studied in the isolated canine heart.
We examined pulsus alternans in seven isolated, perfused canine left ventricles ejecting into a simulated arterial impedance. Left ventricular pressure-volume loops were measured during pulsus alternans while filing-source pressure was lowered. In all cases two distinct linear end-systolic pressure-volume relationships (ESPVRs) were noted for the strong and weak beats. The slopes of the ESPVRs of the strong beats were significantly greater than those of the weak beats (mean difference 0.9 +/- 0.6 mm Hg/ml, p less than .01), while the intercepts were not significantly different (mean difference 0.06 +/- 0.5 ml). Diastolic pressure-volume relationships for the strong and weak beats were not significantly different, excluding incomplete relaxation as a cause of pulsus alternans. Although the weak beats had both a smaller preceding end-diastolic volume and a larger end-systolic volume, the presence of two distinct ESPVRS for the strong and weak beats shows there is alternating ventricular chamber contractility in pulsus alternans that is not solely due to the Starling mechanism. The magnitude of alternation in pump function parameters such as pressure and stroke volume during pulsus alternans reflects the complex interactions of alternating contractile state with alternations in preload and afterload.
Animals↗