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Biomedical subjects

A Frenkel

Publications and source records attributed to A Frenkel.

72 records · Page 4Linked to original sources

Monitoring of 57Co-bleomycin delivery to brain metastases and their tumors of origin.

The concentration of cobalt-57 (57Co)-labeled bleomycin delivered to three brain metastases and to their tumors of origin in the lungs was measured using a single-photon emission computerized tomography technique. In two brain metastases the 57Co-bleomycin concentration measured at different times after the intravenous injection was significantly lower than that in the originating lung tumors (p less than 0.01 and p less than 0.001). In these two patients, the tumor cumulative concentration (TCC) of drug in the brain neoplasm compared to the lung carcinoma was 12.92 versus 15.12 and 10.30 versus 19.74 micrograms/cc/min. In the third patient there was no significant difference in drug concentration between the tumor in the brain and in the lung (TCC 16.02 vs. 15.09 micrograms/cc/min). There was a significant difference in the drug TCC between the three brain metastases: the difference between the lowest and highest concentrations was more than 50% (10.3 vs. 16.02 micrograms/cc/min). When the concentration in the tumor over time (CT(t)) of the 57Co-bleomycin was compared in the brain and lung tumors, a good correlation was found in each of the three cases (r = 0.93, 0.99, and 0.97). This suggests that the difference in drug uptake between brain metastases and their originating lung tumor is a quantitative rather than a qualitative phenomenon. The results show that the amount of drug to which brain metastases are exposed varies and may be very low in some tumors; therefore, effectiveness of drug delivery may play a role in the nonresponsiveness of brain metastases to treatment.

Bleomycin↗

T lymphocytes of rheumatoid arthritis patients show augmented reactivity to a fraction of mycobacteria cross-reactive with cartilage.

An acetone-precipitable fraction of Mycobacterium tuberculosis cross-reacts with human cartilage. Immune responses to this antigen were assessed in 34 patients with rheumatoid arthritis, 16 patients with degenerative joint disease, and 15 healthy controls. The RA patients differed from the other two groups in having more pronounced T lymphocyte responses to the antigen; their serum antibody levels were not higher. The responses of RA patients varied with duration of disease. In the first year (7 patients) T lymphocyte reactivity was increased in the synovial exudates of affected joints but not in peripheral blood, whereas the 19 with disease of 1-10 years' duration showed high reactivity in peripheral blood; in the 8 with disease for more than 10 years, lymphocyte reactivity did not differ from that in the patients with degenerative joint disease or the healthy controls. The observation that the three groups did not differ in their responses to streptococci and a T-cell mitogen indicates that reactivity of the RA patients to the mycobacterial fraction was specific. These results raise the possibility that bacterial antigens cross-reactive with cartilage proteoglycans may be relevant to the pathogenesis of RA.

Adult↗

Microsurgical anastomosis of rat carotid arteries with the CO2 laser.

In order to further evaluate the role of lasers in microvascular tissue closure, we modified an existing CO2 surgical laser (Xanar XA-20) by adding a partially reflecting mirror to attenuate the beam. This allowed the laser to operate at an output of approximately 100 mW, which was appropriate to achieve microvascular closures. In each of 43 rats, one carotid artery was transected and then anastomosed with standard suture technique with 10 to 12 simple interrupted sutures of size 10-0 Ethilon nylon suture (Ethicon, Inc.). The opposite carotid in each rat was anastomosed by the placement of three stay sutures followed by the application of laser irradiation to the tissue between the stay sutures at 90 to 100 mW, spot size of 0.2 mm, pulse duration 0.2 seconds, approximately 20 to 30 pulses per anastomosis. In vivo test periods were 1 hour, 1 day, 3 days, 7 days, 10 days, 14 days, 28 days, 91 days, and 180 days. All anastomoses were evaluated for patency, and selected samples were utilized for light microscopy, and mechanical testing (intraluminal pressure raised to 300 mmHg). It was determined that similar patency rates and slightly faster time to perform the same procedure could be achieved with the use of the low-powered CO2 laser. However, histologic evidence of significant medial damage raises concern about the long-term risk of a higher aneurysm rate. Vessel damage and the lack of simple intraoperative methods to verify the quality of the laser technique restrict these authors from advocating the clinical introduction of the procedure until further advances are made.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Improved radionuclide method for assessment of pulmonary artery pressure in COPD.

An improved method of noninvasive assessment of pulmonary arterial pressure is presented. The already existing radionuclide method for assessment of pulmonary arterial pressure based on right ventricular ejection fraction, although having a relatively good positive predictive accuracy (75 percent), lacks in specificity and correlates only weakly with pulmonary arterial pressure, r = .66. In the present study a diastolic index of the ventricular performance (right atrial early diastolic emptying rate) was used to improve the predictive value of the right ventricular ejection fraction. Phase image analysis was used to differentiate the right atrium from the rest of the cardiac structures, and right atrial emptying rate was calculated after time activity curves were generated. A reasonably good correlation was found between right atrial emptying rate and pulmonary arterial pressure, r = .75. This diastolic index, however, was limited in its ability to detect patients with COPD and normal pulmonary arterial pressure (negative predictive value 62 percent). In order to improve the predictive value of right ventricular ejection fraction, having low specificity (33 percent) but high sensitivity (93 percent), a score index was constructed, combining right ventricular ejection fraction with right atrial emptying rate (having high specificity 100 percent, but modest sensitivity 78 percent). Score index proved to be an excellent indicator of pulmonary arterial hypertension (positive predictive value 93 percent, negative predictive value 100 percent.

Adult↗

Arthritis induced by a T-lymphocyte clone that responds to Mycobacterium tuberculosis and to cartilage proteoglycans.

Adjuvant arthritis characterized by chronic inflammation of the joints of rats is induced by immunization to Mycobacterium tuberculosis. To learn how autoimmune arthritis may be caused by a microbial antigen, we isolated a T-lymphocyte clone specific for M. tuberculosis antigens that was strongly arthritogenic. We now report that the clone recognized, in addition to M. tuberculosis antigens, antigens present in human synovial fluid, medium of chondrocyte cultures, and proteoglycans purified from cartilage. These observations indicate that the target antigen for the arthritogenic clone resides in the proteoglycan component of cartilage. As this arthritogenic clone shows specificity for both a M. tuberculosis antigen and a cartilage constituent we conclude that disease is probably caused by antigenic cross-reactivity. Thus, an autoimmune disease may be triggered by structural mimicry between antigens in the environment and self-antigens in the individual.

Animals↗

24-Hour/4-hour ratio of technetium-99m methylene diphosphonate uptake in patients with bone metastases and degenerative bone changes.

The uptake of [99mTc]MDP in metastatic lesions of the vertebrae was compared with the uptake in normal vertebrae. The ratio of these lesion-to-nonlesion uptakes at 4 and 24 hr was called the 24-hr/4-hr ratio (TF ratio). A similar ratio was measured for lesions in the spine due to degenerative bone disease. Lesions in vertebrae with degenerative bone disease and treated metastases had a significantly lower TF ratio than lesions in vertebrae with untreated bone metastases. These findings suggest that the TF ratio might be a reliable method for separating metastatic lesions from degenerative changes in the vertebral column, and could be especially useful in cancer patients whose bone scans demonstrate a single lesion in the spine.

Adult↗

T lymphocyte lines producing or vaccinating against autoimmune encephalomyelitis (EAE). Functional activation induces peanut agglutinin receptors and accumulation in the brain and thymus of line cells.

We studied lines of rat T cells, specifically reactive against myelin basic protein (BP), that were functional in mediating autoimmune encephalomyelitis or in vaccinating rats against induction of active EAE. Herein we report that these functions depended on activation of the cells by incubation with BP or with a T cell mitogen prior to inoculation into recipient rats. Activation was accompanied by the exposure of membrane-binding sites specific for the lectin peanut agglutinin. Accumulation of activated line cells in the central nervous system and thymus gland was observed.

Animals↗

Autoimmune encephalomyelitis (EAE) mediated or prevented by T lymphocyte lines directed against diverse antigenic determinants of myelin basic protein. Vaccination is determinant specific.

Lines of T lymphocytes reactive against the basic protein of myelin (BP) were found in previous studies to mediate experimental autoimmune encephalomyelitis (EAE) in rats. Moreover, inoculation of rats with attenuated anti-BP line cells vaccinated them against subsequent attempts to induce active EAE by injection of BP in adjuvant. In the present study, we investigated the effects of T lymphocyte lines reactive to different antigenic determinants on the BP molecule, they are the major encephalitogenic peptide (EP) determinant present on guinea pig BP (G-BP), and minor, non-EP determinants present on bovine BP (B-BP). We found that both lines of T lymphocytes could mediate EAE. Resistance to active EAE acquired by spontaneous recovery from line mediated EAE or by vaccination with attenuated cells, however, was found to be specific for the particular BP determinant. Thus, EAE may be mediated by lines of T lymphocytes reactive to different determinants on the BP molecule, but the resistance to EAE acquired by exposure to line cells is determinant specific. This suggests that acquired resistance to EAE is directed by the receptor specificity of the autoimmune anti-BP T cells.

Animals↗

Hydrocortisone and inhibitors of prostaglandin synthesis. Potentiation of allograft survival in mice.

We studied the effects on survival of allogeneic skin grafts after treatment with hydrocortisone and/or inhibitors of prostaglandin synthesis: indomethacin and flufenamate. We found a marked synergistic effect of combined treatment with hydrocortisone and indomethacin or flufenamate. Neither hydrocortisone nor indomethacin or flufenamate, when given alone in relatively small doses, caused delayed graft rejection. However, when small doses of hydrocortisone were used in combination with flufenamate or indomethacin, the median survival time (MST) of allogeneic grafts was prolonged from 11.4 days to 20.9 and 23.8 days, respectively. Moreover, the increase in graft survival was comparable to that obtained by treatment with relatively high doses of azathioprine alone or combined with hydrocortisone. The finding of synergism between low doses of prostaglandin synthesis inhibitors and glucocorticoids in delaying graft rejection suggests that such treatment might provide a relatively safer means of achieving clinical immunosuppression than the high doses of steroids and azathioprine currently in use.

Animals↗

Myelopoiesis in the presence of stromal cells from mouse bone marrow: I. Monosaccharides regulate colony formation.

Colony stimulating factor (CSF) was incapable of inducing the formation of granulocyte/monocyte (G/M) colonies in the presence of bone marrow-derived adherent cells. To test the possibility that interactions between adherent cells and myeloid progenitors are mediated via glycoproteins, we added a variety of sugars to methyl-cellulose cultures of BALB/c mouse bone marrow cells, in the presence of syngeneic bone marrow adherent cells. We found that a number of free sugars, as well as certain glycosides, relieved the inhibition of G/M colony formation exerted by the adherent cells. The effect of these monosaccharides was neither due to osmotic changes nor to their toxicity to the adherent cells. It is therefore concluded that glycoprotein or glycolipid factors may be involved in the interactions between myeloid progenitors and stromal cells.

Animals↗

Malignant change in a verrucous nevus.

A 41-year-old man developed squamous-cell carcinoma within a verrucous nevus of linear distribution of a long duration. Controversial cases have been reported in the literature. Such malignant change in verrucous nevus is extremely rare.

Adult↗

Effects of sulfhydryl reagents on basal and vasopressin-stimulated Na+ transport in the toad bladder.

The role of reactive SH groups (presumably in proteins) of the apical plasma membrane in transepithelial Na+ transport was studied in the isolated urinary bladder of the toad. On the basis of assays for TCA-soluble SH compounds (e.g., glutathione, methionine), PCMB, PCMPS, NTCB, and DTNB did not penetrate the intracellular compartment from the luminal media either in control or vasopressin-treated bladders. In contrast, PCMB from the serosal side and NEM from the luminal side titrated significant fractions of the TCA-soluble SH compounds. We conclude, therefore, the PCMB, PCMPS, NTCB, and DTNB are suitable reagents for studies on the physiological properties of apical plasma membrane SH groups. Titration of apical membrane SH groups with PCMPS, NTCB, and DTNB revealed heterogeneity in functional responses: PCMPS and NTCB elicited transient, 25-60% increases in SCC. In substrate-free media, pretreatment with these reagents inhibited the increase in SCC produced by vasopressin or cyclic AMP (+ theophylline). In glucose-enriched media, the responses to combinations of vasopressin and PCMPS or NTCB were additive, implying activation via parallel pathways. Simultaneous addition of vasopressin or cyclic AMP (+ theophylline) and NTCB resulted in marked synergism, presumably as a result of unmasking of SH groups by the the hormone (or the intermediate). These results suggest that basal Na+ transport is regulated in part by SH compounds in the apical membrane that are distinct, although not necessarily different in kind, from those involved in the response to vasopressin.

Amiloride↗