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Biomedical subjects

J Forman

Publications and source records attributed to J Forman.

At least 145 records · Page 8Linked to original sources

Use of H-2 mutations to quantitate alloreactivity: Alloreactivity is strongest against H-2 antigens which are closet to self.

Lymph-node cells from H-2 allogeneic, intra-H-2 recombinant and H-2 mutant congenic strains were sensitized in limiting dilution cultures to quantitate the cytotoxic T-lymphocyte precursor frequencies (CTL.Pf) against antigens encoded by different regions of the H-2 complex. When four H-2Kb mutants of C57BL/6 (B6) were tested, we observed anti-B6 CTL.Pf that were as high or higher than those of recombinant strains which differ from B6 at the K end of the H-2 complex. Relative to strains completely H-2 allogeneic to B6, the CTL.Pf in H-2bm3 and H-2bm5 averaged 40--50 percent, and H-2bm8 averaged 140 percent. Recombinant strains B10.A (4R) and B10.D2 (R103), which differ from B6 at the K end of the H-2 complex, averaged 60 percent of the completely H-2 allogeneic value. Since the mutant and wild-type gene products have no serological and minimal structural differences relative to other alleles at H-2K, these results indicate that the CTL.Pf does not increase with increasing H-2 antigenic disparity between andy two strains. Rather, the data suggests that the T-cell receptor repertoire recognizes those H-2 molecules or determinants closest to self.

Animals↗

The effect on respiratory drive of a prolonged physical conditioning program.

Nine sedentary men 21 to 35 yr of age took part in a physical conditioning program involving regular aerobic exercise over a period of 6 to 8 wk. There was significant improvement in indexes of cardiorespiratory fitness. Ventilatory and mouth occlusion pressure responses to CO2 at rest and during threadmill exercise was measured before and after training. The slopes of the regression VE/PCO2 increased during exercise (p < 0.05), but not significantly at rest. The slopes of the regression of occlusion pressure at 100 ms versus PCO2, (P100/PCO2) did not change significantly at rest or during exercise. The VE/PCO2 and P100/PCO2 did not change from rest to exercise, and showed no relation to indexes of fitness. It is suggested that the low respiratory drive seen in some athletes is not due to the adaptation that results from short-term training. The possibility that long-term training may result in decreased responsiveness to CO2 cannot be excluded.

Adult↗

Relationship of intestinal obstruction to serial plasma carcinoembryonic antigen levels.

Since it has been suggested that colonic obstruction due to carcinoma may play a role in elevations of circulating carcinoembryonic antigen, serial plasma carcinoembryonic antigen levels were studies in 19 patients with intestinal obstruction due to tumor and nontumor causes. Regardless of cause, eight of ten patients with colonic obstruction did not show decreased carcinoembryonic antigen levels after decompression. Two patients with postoperative carcinoembryonic antigen reductions of greater than 40 per cent had ascite removed at operation. Removal of a large volume of carcinoembryonic antigen-rich ascites was thought to contribute to the fall in circulating carcinoembryonic antigen. Six patients with small intestinal obstruction and one patient with large and small intestinal obstruction did not show a reduction in postdecompression carcinoembryonic antigen levels. One patient with Crohn's disease who underwent ileal resection and one with intestinal obstruction due to carcinoma of the ovary who underwent resection at the time of decompression had a greater than 40 per cent reduction in postoperative carcinoembryonic antigen levels. Inflamed intestinal and carcinoma of the ovary are known sources of carcinoembryonic antigen and their removal could explain the decrease in carcinoembryonic antigen. Rehydration, as monitored by plasma osmolality and protein concentration, did not explain changes in plasma carcinoembryonic antigen. Thus, it appears that carcinoembryonic antigen production may play a more significant role in the regulation of circulating carcinoembryonic antigen than the physiopathologic processes associated with obstruction.

Aged↗

T cells recognize minor histocompatibility antigens on H-2 allogeneic cells.

B10.A animals were rendered tolerant to B10.M spleen cells by injection of (B10.A X B10.M)F1 cells into neonates. Adult animals accepted B10.M skin grafts and failed to generate cytotoxic effector cells in vitro against B10.M H-2 antigens. In vivo inoculation of tolerant animals with A.CA spleen cells, followed by in vitro challenge with similar cells, resulted in the generation of cytotoxic effector cells that had specificity for the A strain minor histocompatibility (H)-antigens in the context of the H-2f haplotype. If these animals were boosted in vitro with A strain spleen cells, cross-priming could be demonstrated, whereby the cytotoxic effect was restricted by the H-2a haplotype. These data indicate that at least two sets of T cells co-exist in tolerant animals, one capable of recognizing antigens in the context of the host H-2 haplotype, and the other able to recognize antigens in the context of the tolerated H-2-allogeneic haplotype. Because tolerant animals inoculated with A-strain spleen cells in vivo and boosted in vitro with A.CA spleen cells failed to generate a cytotoxic effect against A.CA, it is unlikely that minor H-antigens need to be processed by host lymphoreticular cells.

Animals↗

H-2 unrestricted cytotoxic T cell activity against antigens controlled by genes in the QA/TLA region.

The specificity of H-2 unrestricted cytotoxic T cells was analyzed in secondary CML responses. A/J strain effector cells, sensitized against A.Tlab lymphoid cells, lysed target cells from strains with differing H-2 haplotypes but all sharing Qa-1b/Tlab alleles; whereas, target cells from strains with Qa-1a/Tlaa were not. When B6.Tlaa animals were in vivo-primed and challenged in vitro with B6 stimulator cells, no cytotoxic effector cell activity was generated. However, if B6.Tlaa animals were primed in vivo with A.BY cells and then rechallenged in vitro with either A.BY or B6 stimulator cells, cytotoxic effector cells were generated that lysed target cells from strains with Qa-1b/Tlab alleles. This suggests that factors in addition to Qa/Tla may play a role in the generation of anti-Qa/Tla effector cell activity. It was also noted that targets from strains with Qa-1a/Tlaa alleles were killed, although to a much lesser extent than the Qa-1b/Tlab targets. SWR anti-DBA/1 efffector cells strongly lysed target cells frrom strains with Qa-1b/Tlab, lysed Qa-1a/Tlaa targets to a lesser extent, and produced no cytotoxic effect on B6.Tlaa target cells. These data suggest that in addition to a CML target antigen associated with Qa-1b/Tlab, there may be an additional specificity recognized by cytotoxic T cells controlled by a gene outside of Qa-1b/Tlab.

Animals↗

Oxygen-assisted exercise in chronic obstructive lung disease. The effect on exercise capacity and arterial blood gas tensions.

Twenty-six patients with severe chronic obstructive lung disease exercised on a treadmill while breathing either room air, supplementary compressed air, or O2. Endurance was significantly increased by O2, but there was no improvement in maximal work rate. No relation was found between increased endurance and the degree of hypoxia, hypercarbia, or acidosis during exercise or the changes in these while breathing O2.

Acidosis, Respiratory↗

Estimates of the precursor frequency of cytotoxic T lymhocytes against antigens controlled by defined regions of the H-2 gene complex: comparison of the effect of H-2 differences due to intra-H-2 recombination vs mutation.

Lymph node cells were sensitized in a limiting dilution assay against B10.D2 (H-2d) and the frequency of cytotoxic T lymphocyte (CTL.P) precursors was determined. A mean CTL.P frequency of 0.047% was observed when responding strains differed from the stimulators at the entire H-2 gene complex. When intra-H-2 recombinant strains were sensitized against B10.D2, lower frequencies of CTL.P were observed. Responding strains that differed from the stimulators at the H-2K-end only had 2- to 6-fold more CTL.P compared to strains sensitized against the D-end only. In order to study the CTL.P frequency against minor antigenic differences, the B10.D2 (M504-H-2da) mutant strain, which carries a mutation with an antigenic gain-loss in the D-region of H-2d, was examined. This mutant showed an identical CTL.P frequency against H-2d as H-2D-end recombinant strains. Therefore, this H-2 mutant (M504) has either undergone extensive mutation or the qualitative nature of the antigenic loss in this strain results in a high CTL.P frequency against the strain of origin.

Animals↗

[Mitral commissurotomy under direct vision. 37 cases].

1 188 mitral commissurotomies were carried out between 1962 and 1976, 37 of them (3.1%) being under direct vision. The two operative deaths (5.4%) occurred early in the series. Longer term follow-up showed that 3 cases died secondarily, and 3 had revision surgery. The main complication was mitral incompetence (51% of operated cases had a systolic murmur). The varying indications and results are presented; these justify a prospective study, but not a recommendation for the systematic adoption of mitral commissurotomy by an open heart technique.

Adult↗

Relationship between trinitrophenol and H-2 antigens on trinitrophenyl-modified spleen cells. III. Quantitative aspects of trinitrophenol binding on cells treated with trinitrobenzene sulfonic acid.

Splenic lymphoblasts or normal spleen cells were treated with varying concentrations of TNBS in order to assess whether cell membrane H-2 molecules were derivatized with TNP. Cells treated with high concentrations of TNBS had their cell membrane H-2 molecules derivatized and functioned antigenically as inhibitors in a cold target TNP-CML competition assay. In contrast, cells derivatized with lower concentrations of TNBS had a significant proportion of their membrane proteins derivatized with TNP but did not have their H-2 molecules derivatized. These latter cells were unable to block anti-TNP cytotoxic effector cells in the competition assay. When cells were treated with 3H-TNBS, it was observed that TNP couples to cell membrane H-2, Ia and Ig molecules, and an estimate of the number of TNP molecules bound per cell at varying concentrations of TNBS was determined. The data obtained are consistent with there being a requirement for TNP to directly derivatize H-2 molecules on the cell membrane in order to create antigenic determinants that can be recognized by cytotoxic anti-TNP effector cells. As an alternative, there may be a requirement for the presence of a high density of TNP molecules per cell rather than direct H-2 derivatization by TNP in order to account for activity.

Animals↗

[Prospective etiologic survey on apparently primary nonobstructive myocardiopathies in adults. 57 cases, excluding ischemic cardiopathies].

A prospective study into the aetiology of presumed primary non-obstructive cardiomyopathy was carried out in 57 patients who had no lesions of the trunk of the coronary artery; one case of haemochromatosis and one of amyloidosis were found. Excluding these two cases of cardiomyopathy which were in fact secondary, most of the others were associated with manifestations or with complications of myocardial diseases (two pulmonary emboli and one case of jaundice) or pathology associated with it. Investigation into possible infection, biochemical abnormalities and dietary indiscretion (alcohol, colza oil), were unfruitful. Electromyographic changes of the "myositic" type were very common. The bicycle ergometry test was often interrupted through fatiguing of the peripheral muscles. These findings suggest that the muscular abnormalities may not be limited to the heart. The cost of an enquiry of this type has been investigated.

Adolescent↗

Cytotoxic T cells distinguish between trinitrophenyl- and dinitrophenyl-modified syngeneic cells.

Spleen cells sensitized against trinitrophenyl (TNP)-modified stimulator cells displayed a cytotoxic effect against syngeneic TNP-modified but not dinitrophenyl (DNP)-modified target cells. The same finding was observed in the opposite direction; that is, effector cells sensitized against DNP-modified stimulator cells did not cross kill TNP-modified targets. The specificity of the anti-TNP effector cells was confirmed in a cold target competition assay. Presensitization in vivo with hapten-modified cells followed by rechallenge and testing in vitro did not alter the specificity of the response between the haptens. These data indicate that the receptor(s) on the cytotoxic T cell can distinguish between two closely related haptenic molecules.

Animals↗

[Subvalvular aortic stenosis, dysmorphic familial syndrome and peripheral muscular disease].

Two related cases are reported, those of two sisters aged 7 and 13, who had an aortic subvalvular stenosis in the form of a fibro-muscular channel, associated with mitral incompetence, a triangular facies with a pointed chin, pinched lips, a divergent squint, hypertelorism, a mask-like face, normal intelligence, and a peripheral muscular disorder with arthrogriposis. The description of such a combination of malformations is original, and this is discussed.

Abnormalities, Multiple↗