Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) are critical in the development of an effective immune response. Vitamin D, essential in short-term calcium homeostasis and recently shown to modulate proliferation and function of blood mononuclear cells from adult dairy cattle, may be an effective modulator of the calf's immune system. Effects of antigen sensitization and 1,25-dihydroxyvitamin D3[1,25-(OH)2D3] on cytokine secretion by cells from calves vaccinated with Bacille Calmette-Guérin (BCG) were examined. One-week-old dairy calves (n = 6) and yearling heifers (n = 4) were vaccinated concurrently with BCG and boosted six weeks later. Ten weeks after primary vaccination, cells from vaccinated calves and adults, and nonvaccinated, age-matched calves (n = 4) were evaluated in vitro for their capacity to produce IFN-gamma and TNF-alpha. Cells were stimulated with pokeweed mitogen (PWM) or recall antigen [Mycobacterium bovis-derived purified protein derivative (PPD)] in the presence of 0, 0.1, 1.0, and 10 nM of 1,25-(OH)2D3 for 20, 44, and 68 hours, respectively. IFN-gamma and TNF-alpha concentrations in culture supernatants harvested at these times were quantified by enzyme-linked immunosorbent assay (ELISA). PPD-induced IFN-gamma and TNF-alpha responses of cells from vaccinated calves and adults were greater than responses of autologous unstimulated cells. In contrast, PPD-specific responses of calf and adult cells collected immediately before primary vaccination were substantially lower and comparable to responses in resting (i.e., unstimulated) cultures. At ten weeks, the PPD-specific response of vaccinates exceeded the response of nonvaccinated calves; however, responses of vaccinated calves were more vigorous than corresponding responses of vaccinated adults. Incubation period also influenced the magnitude of both IFN-gamma and TNF-alpha, responses in PPD- and PWM-stimulated cultures. Effects of 1,25-(OH)2D3 on antigen-induced secretion of IFN-gamma and TNF-alpha were marginal. Only IFN-gamma responses of vaccinated adults were affected by 1,25-(OH)2D3. Vitamin D caused a concentration-dependent decrease in IFN-gamma response and an increase in TNF-alpha response in PWM-stimulated cultures. These results indicate that animal maturity (i.e., age) and antigenic experience affect IFN-gamma and TNF-alpha secretion by bovine leukocytes and suggest that 1,25-(OH)2D3 can alter secretion of both cytokines under specific conditions of culture.

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Left heart catheterization by puncture of the atrial septum was introduced by Manfredi (1956) and elaborated by Ross (1959). We have investigated 65 patients by this method and present our results with particular reference to its safety and effectiveness.SUBJECTS AND METHODThe majority of the patients had rheumatic heart disease ( Table I). The age range was 9 to 67 years and the distribution is shown in Table II. There were three patients under 17 years of age. The size of the left atrium was graded on X-ray (penetrated postero-anterior, right lateral, and right anterior oblique views with barium in the cesophagus) and was found to be normal in 11, slightly enlarged in 23, moderately enlarged in 29, and aneurysmal in 2 patients.The basic technique of transseptal left atrial puncture used was that described by Ross, Braunwald, and Morrow (1960). Briefly, this consists of introducing a 595 cm. long catheter into the right atrium from the right saphenous vein, threading the 61 cm. transseptal needle (Fig. 1) through the catheter and puncturing the septum in the region of the fossa ovalis with the needle. It has not always been found possible to make contact with the atrial septum in the lower half of the right atrial shadow as advised by Ross since a small left atrium frequently lies higher. When this is the case it is considered especially important to maintain the 450 posterior slant of the needle at puncture since the aorta is at the same level but anterior to the left atrium.The entire procedure is done under fluoroscopic control, and blood samples and pressure pulses are taken through the needle immediately before and after the puncture to confirm the position of its tip.When, in ten of the earlier cases of the series, information was required from the left ventricle as well as the atrium, an attempt was made to obtain it by passing a thin polythene tube through the needle once its tip was lying in the left atrium . This procedure was unsatisfactory in our laboratory and was abandoned in favour of advancing the large catheter over the needle after the tip of the needle has been introduced into the atrium. The procedure evolved in our laboratory whereby the needle is held stationary while the catheter is advanced differs slightly from that described by Brockenbrough and Braunwald (1960) and Gorlin et al. (1961) in which the needle and catheter are advanced together for a short distance with the needle point protruding before the catheter is further advanced over the needle. Once the catheter is in the left atrium the needle is withdrawn to the point of puncture and the catheter advanced into the ventricle. The needle is then removed and all the pressure measurements under rest and exercise conditions and the blood samples required in the individual case are obtained, and contrast injection is performed if indicated.When right heart catheterization was indicated it was performed through the same vein either after the left heart catheterization (40 patients) or simultaneous with it (6 patients). The bleeding tha...

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