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Biomedical subjects

K Joseph

Publications and source records attributed to K Joseph.

At least 19 recordsLinked to original sources
PubMed1992

Effects of phorbol myristate and ionomycin on in vitro growth of aged Peyer's patch T and B cells.

The proliferative responses of Peyer's patch (PP) T cells from aged BALB/c mice to concanavalin A (Con A) are considerably reduced, as compared to those of the young (P < 0.001). This reduced reactivity of aged T cells could be partly, but not entirely, corrected by interleukin 2 (IL-2) (P < 0.001). PP T cells from aged mice responded synergistically to a protein kinase C (PKC) activator, phorbol myristate acetate (PHA), plus a calcium ionophore, ionomycin, at much lower concentrations than to Con A (P < 0.001); however, the maximal proliferative response still remained nearly at 8/10th of the young (P < 0.01) and higher levels of PMA (but not of ionomycin) were required (P < 0.001). Addition of IL-2 restored the diminished response to the levels of the young T cells (P < 0.05), but that of Con A did not (P > 0.05). The proliferative responses of PP B cells to lipopolysaccharide (LPS) do not differ from those of the young (P > 0.05), but the spontaneous proliferation of aged (unstimulated) B cells is enhanced nearly twofold versus that of the young (P < 0.001). Like the PP T cells, PP B cells from aged mice also responded synergistically to PMA plus ionomycin but to a lesser degree than those of the young under the same stimulation (P < 0.01). Their maximal proliferation required higher levels of PMA, but not of ionomycin and was also diminished (P < 0.01), compared to that of the young. B cell stimulatory co-factors, IL-4 and IL-6, failed to affect the response of aged and young B cells to PMA plus ionomycin (P > 0.05), whereas LPS remediates the reduced response of aged B cells to PMA plus ionomycin. Thus, T and B cells from senescent PP demonstrate an impaired proliferative responsiveness via the Ca-dependent PKC pathway. A T cell mitogen and B cell stimulatory cytokines did not alter this activation pathway, once optimally stimulated. Whereas, T cell stimulatory cytokine IL-2 and B cell mitogen LPS could restore the age-associated decline of the corresponding lymphocyte subsets, T and B cells, in activation of the Ca-dependent pathway. The altered transmembrane signal transduction appears to be intrinsically defective in these aged PP T and B cells.

Aging↗
PubMed1992

Hemophan versus hemophan--a philippic against the suggestion of constant membrane quality.

All statements referring to biocompatibility of dialyzers depend on the suggestion of a constant and reproducible structure of the investigated membrane material. The data presented here strike this concepts in case of hemophane. Two commercially available hemophane dialyzers, the GF MC 120 (Gambro) and the MO 450 (SMAD) membranes, were compared. Significant differences could be seen in the induction of leukopenia and leukocyte sequestration reaction within patients lungs, but also in capacity to influence granulocyte oxidative metabolism and release of granular enzymes. According to these data it seems questionable whether hemophane is a membrane material with constant structure and quality normally expected for products bearing trade names. Excluding other differences (like surface-area or sterilization method) variable amounts of DEAE substituents and/or an inconstant distribution of the DEAE groups within the membranes may be the most possible reason responsible for the differences found. The study underlines the urgent need of an exact physico-chemical characterization of dialyzer membranes and is therefore a challenge for free publication of such basic data by the producers.

Biocompatible Materials↗
PubMed1991

Early developmental profile of ornithine decarboxylase in the frog, Microhyla ornata and its regulation by polyamines.

Ornithine decarboxylase (ODC) activity and polyamine levels were measured during early development of the frog, Microhyla ornata. ODC activity was found to be high and it showed three major peaks during the first 60 hr of development. Putrescine and spermidine levels increased gradually during the above period with little change in spermine. Treatment of developing embryos with exogenous putrescine and spermidine prevented the normal increase in ODC activity. Spermine did not have any significant effect. Addition of ornithine also prevented the increase in ODC activity. Experiment using exogenous ornithine and alpha-methylornithine revealed that formation of putrescine and/or spermidine from ornithine is necessary for the suppression of ODC to occur. Suppression of ODC takes place even if conversion of putrescine to spermidine is blocked, indicating that putrescine, independent of its conversion to spermidine, also plays a role in ODC regulation.

Animals↗
PubMed1991

Assessment of ventricular function with first-pass radionuclide angiography using technetium 99m hexakis-2-methoxyisobutylisonitrile: a European multicentre study.

In the context of a multicentre study on the use of technetium 99m hexakis-2-methoxyisobutylisonitrile (99mTc-Sestamibi), we evaluated the accuracy of the ventricular function assessed at rest by means of first-pass radionuclide angiocardiography acquired during the injection of the tracer for myocardial perfusion scintigraphy. The results were compared with first-pass studies performed using reference tracers sodium pertechnetate Tc 99m or technetium 99m diethylene triamine penta-acetic acid or with gated radionuclide angiocardiography. A total of 66 patients of the 105 enrolled in the study could be evaluated. The comparison of the first-pass studies was possible in 33 subjects with regard to the left ventricular ejection fraction, yielding r = 0.909 (P less than 10(-6)), and in 22 cases with regard to the right ventricular ejection fraction, yielding r = 0.712 (P less than 0.001). The comparison between the first-pass study using 99mTc-Sestamibi and the equilibrium gated radionuclide angiocardiography was possible for the left ventricular ejection fraction in 26 cases, with r = 0.937 (P less than 10(-6)), and for the right ventricular ejection fraction in 15 subjects, with r = 0.783 (P less than 0.001). In conclusion, the assessment of ventricular function performed by acquiring a first-pass radionuclide angiocardiograph during the injection of 99mTc-Sestamibi for perfusion myocardial scintigraphy can be considered reliable and accurate, when compared with the usually employed techniques. This result confirms the feasibility of a combined evaluation of perfusion and function at rest and during stress testing, which represents one of the most interesting advantages offered by the use of 99mTc-Sestamibi.

Coronary Disease↗
PubMed1991

IL4, IL5 and IL6-mediated regulation of immunoglobulin (Ig) heavy chain class switching and Ig production by gut-associated lymphoid tissue (GALT) B cells from athymic nude (nu/nu) mice.

Gut mucosal immunoglobulin (Ig) isotype expression and secretion are known to be regulated by B cell-stimulatory factors (BSF), lymphokines or cytokines from T and non-B cells. The class and amount of Ig secreted appear to depend on the presence of a combination of these factors. The effects of IL-4 and IL-5 on Ig class switching by gut mucosal B cells remain controversial. To shed further light on this issue, young (1-2 months old) athymic nu/nu murine GALT B cells were chosen, because the possibility of in vivo effects of T cells on B cells (in particular at the levels of transcription and translation without changes in surface Ig phenotype expression) cannot be excluded. The results are summarized below. IL-4, IL-5 and IL-6 alone or in combination do not act as IgA heavy chain switch cofactors, but IL-5 and IL-6 do act at least as B cell terminal differentiation factors for any isotype-specific gut-associated lymphoid tissue (GALT) (mesenteric lymph node) B cells in the presence or absence of LPS. The BSF have augmenting effects on class-specific Ig production by GALT sIgM-bearing B cells, when these are treated with the BSF alone. IL-4 alone or in combination with other BSF prevents LPS-stimulated IgM production. BSF without LPS do not evoke production of significant amounts of IgG and IgA by high density (HD) and low density (LD) sIgM-bearing B cells; IgM is synthesized only in small amounts of LD sIgM-bearing B cells in the presence of IL-5 and/or IL-6. There is no difference in the responsiveness of GALT and spleen sIgM-bearing B cells to the BSF.

Animals↗
PubMed1990

Kinetics of pulmonary leukocyte sequestration in man during hemodialysis with different membrane-types.

Although it has been suggested that pulmonary sequestration of leukocytes could account for membrane-dependent white blood cell depletion in HD, direct evidence in patients is still lacking. Therefore a study was initiated to test whether and how leukocytes distribute in the lung circulation during HD with different membranes. Thirteen patients suffering from chronic renal failure underwent lung scintigraphy during HD with cuprophane (n = 3), hemophane (n = 8) and polysulfone (n = 2) lowflux capillary dialyzers. Isolated autologous leukocytes were labelled with 99m-Technetium and reinfused before starting HD. Distribution of leukocyte related activity was registered by lung scintigraphy. In comparison to normal lung scintigraphy performed without HD, an impressive redistribution peak was demonstrated 10-20 min after the start of HD with cuprophane and also to a lesser extent with hemophane. When HD was performed with polysulfone the decrease in activity was delayed but no real redistribution was obtained. In accordance with other phenomena, such as peripheral leukopenia and changes in granulocyte oxidative metabolism, pulmonary sequestration of leukocytes takes place in man in the initial phase of HD and appears to be strongly dependent on the type of membrane.

Humans↗
PubMed1990

[99mTc-2-methoxy-isobutyl-isonitrile in the diagnosis of coronary heart disease: results of a multicenter study].

A total of 226 patients was studied in a phase-III multicenter trial to compare the results of stress/rest 99mTc-MIBI with 201TI scintigraphy and/or coronary arteriography. The evaluation of planar and SPECT imaging was based on a semiquantitative visual scoring. A congruent diagnosis was generated from all planar 201TI and 99mTc-MIBI scintigrams performed in 36 patients. In 62 of 63 patients, SPECT-studies with 99mTc-MIBI and 201TI led to an identical diagnosis. In one patient a positive result was obtained with 201TI-SPECT whereas 99mTc-MIBI was negative. Segmental agreement for 1509 SPECT segments was 85.7%, for 554 planar segments it was 86.6%. In comparison to coronary arteriography, performed in 180 patients, the overall sensitivity for the correct diagnosis of coronary artery disease (CAD) was 86% for planar MIBI scintigraphy or 92% for MIBI-SPECT. Overall specificity was 100% for planar imaging and 57% for SPECT. The low specificity of MIBI-SPECT was probably due to high prevalence of CAD in this study population. In a subgroup of 43 patients, who underwent coronary angiography, identical results were found with 99mTc-MIBI and 201TI. Only one patient showed a positive scintigraphic result with both 99mTc-MIBI and 201TI without angiographically proven stenosis greater than 50% or prior myocardial infarction. Vessel sensitivities in stenosed coronary arteries (greater than 50% stenosis) were 54% for the LAD and 87% for the RCX/RCA areas with MIBI-SPECT, or 51% or 79% for planar scintigraphy, respectively. Vessel specificities for SPECT were 65% in the LAD or 52% in the RCX/RCA, or 90% or 83% in planar imaging.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Effect of fenofibrate on fibrinogen concentration and blood viscosity. Consequences for myocardial microcirculation in coronary heart disease?].

The effect of fenofibrate (a clofibrate derivative) on fibrinogen concentration, blood viscosity and myocardial microcirculation was examined in 35 patients with coronary heart disease (n = 27) or hypertension (n = 8). After eight weeks' administration of 250 mg fenofibrate daily cholesterol and triglycerides levels decreased significantly, as did the fibrinogen concentration, from a mean of 300.7 +/- 75.1 mg/dl to 252.3 +/- 61.2 mg/dl (P less than 0.01). Plasma viscosity and erythrocyte aggregation were also significantly lowered (from 1.43 +/- 0.09 to 1.37 +/- 0.07 mPas and 15.0 +/- 3.1 to 13.5 +/- 2.2, respectively; P less than 0.01). In eight of twelve subjects selected from the whole group thallium myocardial scintigraphy demonstrated, after eight weeks of treatment with fenofibrate, a global (in two) or regional (in six) increase in blood flow. Reduction of fibrinogen concentration may in coronary heart disease achieve an improvement in myocardial microcirculation with decreased myocardial ischaemia.

Blood Viscosity↗
PubMed1989

Granulocyte-related bioincompatibility of hemodialysis: inhibition of oxidative metabolism, degranulation reaction, enzyme release and leukocyte sequestration in the lung.

Hemodialysis (HD) induced contact of granulocytes with cuprophan and modified cuprophan, i.e. hemophan, membranes leads to over-stimulation of their oxidative metabolism. This is shown by the fact that after starting HD the peripheral granulocytes are less stimulable to chemiluminescence (CL) and peroxide production (cytochrome C reduction). Such alterations are likely to be connected with a granular staining loss, enzyme release and sequestration of granulocytes in the lung, which coincides with reported clinical features like dyspnoea and drop in arterial oxygen pressure. HD with polysulfone membranes causes a degranulation reaction too, but does not produce granulocyte inhibition and pulmonary sequestration of leukocytes, clearly indicating that these phenomena strongly depend on the different dialyzer membranes.

Biocompatible Materials↗
PubMed1988

In vivo labelling of granulocytes with 99mTc anti-NCA monoclonal antibodies for imaging inflammation.

We looked for inflammatory lesions in 45 patients using in vivo labelled granulocytes. For the purposes of cell labelling we used a murine, monoclonal antibody reacting with NCA and CEA (BW 250/183) (Bosslet et al. 1985) labelled with 99mTc-pertechnetate. All abscesses and other inflammatory lesions were visualized with excellent quality scintigrams between 2 and 6 h after the injection. As the antibody can be stored in a freeze-dried form and labelled at any time in any Department of Nuclear Medicine with 99mTc-pertechnetate, without cell isolation being necessary, the method appears to be suitable even for use in acute diagnosis. No side-effects have so far occurred, even in patients injected up to three times.

Antibodies, Monoclonal↗
PubMed1988

Imaging of inflammation with granulocytes labelled in vivo.

We have looked for inflammatory lesions in 37 patients using granulocytes labelled in vivo. For the purpose of cell labelling we used a monoclonal murine antibody reacting with NCA and carcinoembryonic antigen (CEA) (BW 250/183) labelled with 99Tcm. All abscesses and other inflammatory lesions were visualized with excellent quality scintigrams between 2 and 6 h after the injection. As the antibody can be stored in a freeze-dried form and labelled at any time in any department of nuclear medicine with 99Tcm without cell separation being necessary, the method appears to be suitable even for use in acute diagnosis. No side effects have so far been found.

Antibodies, Monoclonal↗