Biomedical subjects
Publications and source records attributed to D A Clark.
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The influence of the estrous cycle on the localization of plasma cell precursors in the genital mucosa was studied in CBA/J female mice by using an adoptive transfer system. Within 24 hr after transfer, [3H]-thymidine-labeled donor mesenteric lymph node (MLN) cells were observed in maximum number in proestral and estral cervices and vaginae (14.4 and 9.7 labeled cells/100 mm2 of tissue, respectively), and approximately 60% of these cells contained IgA and 25% IgG. During metaestrus and diestrus, however, few labeled MLN cells (4.0/100 mm2 of tissue) localized in the genital tract and this reduction affected the IgA-containing plasmacyte population in particular. In contrast, no change was noted in the frequency of labeled cells containing IgA in the small intestine over the course of the estrous cycle, although small but significant changes were noted in the frequency of labeled cells producing IgG. These results indicate that the hormonal changes during the estrous cycle may affect the localization of IgA plasma cell precursors in the genital tract and thus may alter the local mucosal immune response in this site.
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The fetus resulting from an allogenic (interstrain) mating represents a type of graft that is not rejected by the mother. Nevertheless, the maternal immune system seems to recognize and to react to the presence of the fetus in a number of ways. One such manifestation is significant enlargement of the lymph nodes that drain the uterus (DLN) of pregnant rodents. We have tested the DLN lymphocytes of mice for reactivity to paternal H-2 alloantigens after interstrain mating. The DLN lymphoid cells obtained from pregnant mice killed fewer newborn F1 recipients in a graft-vs-host mortality assay, and generated less cytotoxic T cell activity against paternal H-2 antigens both in vivo and in vitro. In vitro mixing experiments demonstrated the presence of a cell-associated suppressor activity in the DLN of pregnant mice. This suppressor proved resistant to treatment with mitomycin C, and appeared in the DLN early in pregnancy.
Ergonovine maleate (Ergotrate) was given to 57 patients undergoing coronary arteriography for investigation of angina occurring at rest or without provocation when routine study showed normal arteries or insufficient occlusive disease to explain their symptoms. This provocative test induced coronary arterial spasm in 13 patients, 10 of whom had definite Prinzmetal's angina. The spasm was easily reversed with sublingually administered nitroglycerin. The spasm was occlusive or nearly occlusive in nine patients, and there was associated reproduction of the chest pain and S-T elevation similar to the spontaneous episodes. One patient with Prinzmetal's angina had S-T depression rather than elevation in association with the chest pain. The other three patients without Prinzmetal's angina had focal narrowing without coronary occlusion, reproduction of the chest pain or electrocardiographic changes. Of the 44 patients who did not demonstrate coronary spasm in response to ergonovine, 29 had normal coronary arteries and 15 had various degrees of atherosclerotic occlusive disease. We conclude that cautious administration of ergonovine maleate during coronary arteriography can be safely used to elicit coronary spasm in some patients who have insufficient fixed occlusive disease to explain their symptoms.
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Coronary artery spasm was induced by intravascular administration of ergonovine maleate (Ergotrate) during cardiac catheterization. In 78 patients suspected to have Prinzmetal's angina, no morbidity or death has resulted despite complete occlusive spasm in two and three coronary arteries. Typical EKG changes and akinesia of the myocardium in the distribution of the occluded vessels documented functional myocardial ischemia during spasm. The occlusive spasm is readily reversed by sublingual or intravascular nitroglycerin, and ventricular contractility returns to normal following relief of spasm. Occlusive spasm has been demonstrated in 15 patients with clinical evidence of Prinzmetal's angina. Symptoms have been effectively relieved by coronary vasodilators in 10 patients. Of the 5 patients in whom medical therapy failed, 4 were treated surgically. These 4 patients were in the intensive care unit with protracted, prolonged pain, subendocardial infarctions, and persistent failure of coronary vasodilators. Aorta-coronary bypass grafts have been combined with total cardiac denervation by autotransplantation (one patient) and total cardiac denervation by stripping of the great vessels (3 patients). Two of the patients treated by cardiac denervation died in the early postoperative period. The patient treated by autotransplantation has total relief of symptoms but persistent spasm on angiography. The angiographic demonstration of occlusive coronary spasm remains a valuable diagnostic tool to document definitively the presence of spasm. The surgical results question the value of surgical intervention in this disease.
Body composition was measured in 38 young men all of whom were overweight by standard height-weight tables. The techniques used were body volumetry, determination of total body water by tritium dilution, whole body 40K counting, and anthropometric measurements required for an equation by Wright and Wilmore, the biceps-height formula, and a complex anthropometric model. Body volumeter and total body water dilution results agreed closely. 40K counts gave lower means for the lean mass (higher means for fat mass and percent body fat), while the Wright-Wilmore equation and complex anthropometric model gave high mean values for lean mass (low means for fat mass and percent body fat). Among the five methods correlation coefficients ranged from 0.81 to 0.94 for lean body mass, from 0.74 to 0.89 for fat mass, and from 0.60 to 0.86 for percent body fat. Although all subjects were overweight, only six (16%) were obese.
The times of the first stool and the first void were recorded for 500 infants. The population studied was defined in terms of gestational age, maternal premedication, and mode of delivery. The results are presented in tabular form by time segments with term, preterm, and postterm infants treated separately.
This study assess the effects of oral BCG, as a single agent, on tumor progression and on cell-mediated immune function in patients with metastatic malignant melanoma. Thirty patients were studied including 22 with measurable metastatic lesions and 8 with no detectable disease, following treatment of metastases by surgery, radiotherapy, or 5-(3, 3-dimethyl-1 -triazeno)-imidazole-4-carboxamide (DTIC; DIC). Oral BCG was given in doses of 120--240 mg, 1--3 times per week for periods ranging from 9 to 80 weeks and to total doses of from 1.2 to 20.1 gm. Patients were assessed by direct measurements of tumor mass, PPD skin test and in vitro blastogenic responses to PPD PHA. Of the 22 patient with measureable disease, 19 showed tumor progression and none showed regression of any lesion. Of the 8 without apparent disease, 5 remained stable and 3 had tumor recurrence. Of the total group of 30 patients, 8 showed some increased sensitivity to skin testing with PPD. Of 19 tested, 3 showed an increased PPD response in vitro, while 3 showed a decreased response. Six of 20 tested showed an increased PHA response in vitro. Oral BCG alone was not effective as an antitumor agent in patients with metastatic malignant melanoma.
Target cell lysis by sensitized cytolytic T lymphocytes (CTL) may be conveniently quantitated by 51Cr release. By fitting to the formula, P (% specfic release) = 100 (1-e-Nat) one obtains alpha, the relative frequency of CTL in N lymphoid cells. Using a microassay and murine sarcoma target cells, we observed an unexpected decrease in lysis whenever effectors obtained from a graft-vs-host reaction were tested at high concentrations. This inhibition was not observed with CTL generated by an MLC reaction. Inhibition could not be explained by nonspecific mechanical 'crowding', reutilization of released isotope, suppression of release from dead target cells, or the particular strain combination and target used. By modifying the formula to allow suppression of CTL by a stochastic cell-cell interaction with suppessor cell, we found that P = 100 (1-e-Nate-Ngamma) adequately fitted the data, where Ngamma is proportional to inhibitor content. An 18- to 24-hr incubation at 37 degrees C but not 4 degrees C allowed selective depletion or enrichment of inhibitors; in mixing experiments, both parameters Nalpha t and Ngamma behaved stoichiometrically as independent cellular properties. The inhibitor was resistant to concentrations of anti-T cell (RAMG) serum + complement which killed -TL. A similar inhibitor arose in vivo during an anti-tumour allograft response. The ability to quantitate CTL and inhibitor activities from titration curves provides a technique for studying the identity and mechanism of suppressor cells acting at the effector stage of cell-mediated immunity.
Serum cholesterol and urate levels were measured in 150 young men at 2- to 4-month intervals during their first 18 months at the U.S. Air Force Academy. During the first week of cadet training, mean serum urate levels rose as high as 9.5 mg/100 m/, but decreased after a Sunday break. During this week, urate levels in excess of 8.49 mg/100 m/ were found in 44% of the subjects. Such levels, while definitely exceeding normal limits, were attributed to acute psychosocial stress rather than to an abnormal or pathological process. One month after the completion of basic military training, mean serum urate levels were within normal limits, as were all subsequent mean urate levels. Mean serum cholesterol levels were elevated at three times - during the first week of training, after the first month of the first academic year, and during a week of intense military training in the following spring. Apparently, urate and cholesterol levels were elevated by different aspects of stress. Elevations of uric acid level appeared to reflect stress that excited fear or insecurity. Elevations of cholesterol levels apeared to reflect a stress which the individual perceived as requiring a sustained increase in physical and/or mental performance.
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