Citation Information: J Clin Invest. 1977;60(3):555-562. https://doi.org/10.1172/JCI108807.
Abstract
To estimate the relative contribution of l-triiodothyronine (T3) and l-thyroxine (T4) to thyroidal effects, we have measured the concentration of iodothyronine bound to specific hepatic nuclear receptor sites by three different techniques: (a) specific radioimmunoassay after separation of T3 and T4 by preparative paper chromatography; (b) in vivo kinetic approaches as reported previously; and (c) isotopic equilibration. By these three methods, receptor concentration of T3 and T4 in liver was 0.51±0.19 (SD) and 0.08±0.06; 0.52±0.12 and 0.08±0.02; and 0.50±0.13 and 0.10±0.03 pmol/mg DNA, respectively. The percentage contribution of T3 and T4 to total receptor iodothyronine was thus 86.8±9.0 and 13.2±9.4; 86.3±3.5 and 13.7±3.5; and 83.7±5.6 and 16.3±5.6%, respectively. In kidney, specifically bound nuclear T3 and T4 were estimated both by isotopic equilibration and by in vivo kinetic techniques to be 0.28±0.11 and 0.03±0.01 pmol/mg DNA, respectively. Thus, T3 constituted 89.4±3.2% of total receptor iodothyronine in this tissue. No other iodothyronines or analogs were bound to the nuclear sites in either tissue. Kidney and liver nuclear T3 concentrations also were identical to values previously reported with in vivo kinetic techniques. Other studies from this laboratory have suggested that thyroid effect is related to the molar concentration of iodothyronine bound to specific nuclear sites, that the sites are similar in various tissues, and that iodothyronine in plasma is in equilibrium with nuclear T3. If these relationships are assumed, T3 contributes between 85 and 90% of thyroidal effects in the euthyroid rat. The remaining 10-15% of thyroidal effect appears to result from the intrinsic activity of T4.
Authors
Martin I. Surks, Jack H. Oppenheimer
Citation Information: J Clin Invest. 1977;60(3):595-610. https://doi.org/10.1172/JCI108811.
Abstract
18 patients with idiopathic pulmonary fibrosis were studied to determine if they had morphologic evidence of small airways disease and if physiologic testing could predict morphologic findings. In the presence of normal airway function by standard physiologic studies (forced expiratory volume in 1 s/forced vital capacity and airway resistance by plethysmography), dynamic compliance, maximum expiratory flow-volume curves, and maximum flowstatic recoil curves were measured to detect physiologic alterations consistent with small airways abnormalities. These physiologic data were then compared with estimates of small airways diameter made in lung biopsy specimens.
Authors
Jack D. Fulmer, William C. Roberts, Edwyna R. von Gal, Ronald G. Crystal
Citation Information: J Clin Invest. 1977;60(3):611-619. https://doi.org/10.1172/JCI108812.
Abstract
To assess the role of circulating immune complexes in the pathogenesis of acute rejection, sera were measured for such complexes by the 125I-C1q binding assay in 45 normal subjects, 24 allografted patients undergoing acute rejection, and in 11 allografted patients in a quiescent phase. Increased C1q-binding activity (C1q-BA) was detected in 14 patients with acute rejection, 9 of whom had renal biopsies showing fibrin deposition in the vasculature together with cellular infiltrates in the tubulo-interstitial structures; renal histology was not available in the other 5 patients. The other 10 patients with acute rejection, whose biopsies showed only cellular infiltrates, and the 11 patients in a quiescent phase posttransplantation did not have increased levels of serum C1q-BA.
Authors
Yuet M. Ooi, Boon S. Ooi, Enrique H. Vallota, Martin R. First, Victor E. Pollak
Citation Information: J Clin Invest. 1977;60(3):620-625. https://doi.org/10.1172/JCI108813.
Abstract
The association of potassium (K) depletion with polyuria and a concentrating defect is established, but the extent to which these defects could be secondary to an effect of low K on water intake has not been systematically investigated. To determine whether hypokalemia has a primary effect to increase thirst and whether any resultant polyuria and polydipsia contribute to the concentrating defect, we studied three groups of rats kept in metabolic cages for 15 days. The groups were set up as follows: group 1, normal diets and ad lib. fluids (n = 12); group 2, K-deficient diet on ad lib. fluids (n = 12); and group 3, K-deficient diet and fluid intake matched to group 1 (n = 14). Daily urine flow and urinary osmolality of groups 1 and 3 were not significantly different throughout the study. In contrast, as of day 6, group 2 rats consistently had a higher fluid intake (P < 0.0025), higher urine flow (P < 0.001), and lower urinary osmolality (P < 0.001) than the other two groups. These alterations in fluid intake and urine flow preceded a defect in maximal concentrating ability. On day 7, maximal urinary osmolality was 2,599±138 msmol/kg in rats on K-deficient intake and 2,567±142 msmol/kg in controls. To determine whether this primary polydipsia is itself responsible for the development of the concentrating defect, the three groups of rats were dehydrated on day 15. Despite different levels of fluid intake, maximal urinary osmolality was impaired equally in groups 2 and 3 (1,703 and 1,511 msmol/kg, respectively), as compared to rats in group 1 (2,414 msmol/kg), P < 0.001. We therefore conclude that K depletion stimulates thirst, and the resultant increase in water intake is largely responsible for the observed polyuria. After 15 days of a K-deficient diet, the impaired maximal urinary concentration in hypokalemia, however, was not related to increased water intake, since fluid restriction did not abolish the renal concentrating defect.
Authors
Tomas Berl, Stuart L. Linas, Gary A. Aisenbrey, Robert J. Anderson
Citation Information: J Clin Invest. 1977;60(3):626-638. https://doi.org/10.1172/JCI108814.
Abstract
The phytohemagglutinin (PHA) response of lymphocytes from untreated patients with systemic lupus erythematosus (SLE) was studied using highly purified subpopulations of cells involved in the transformation response: T lymphocytes, B lymphocytes, and monocytes. Cell transformation was quantitated using both tritiated thymidine ([3H]-TdR) incorporation into DNA and cytofluorographic determination of cellular DNA content. Dose-response curves using six concentrations of PHA and five concentrations of cells over 0-5 days revealed a decrease in [3H]TdR by stimulated lymphocytes from some SLE patients. This decrease in [3H]TdR was paralleled by a decreased percentage of cells in S, G2, and M phases of the cell cycle. However, abnormal response occurred entirely in those SLE patients who were hypocomplementemic. The etiology of the impaired response was further examined. Lymphocyte receptors for concanavalin A were studied using cytofluorography of lymphocytes stained with fluorescein-conjugated concanavalin A. The frequency distribution of concanavalin A receptors was similar in the normocomplementemic and hypocomplementemic lupus patients and in normals. The latex phagocytic activity of lupus macrophages was similar to normals when allogeneic normal plasma was used in the culture medium. Phagocytic activity became abnormal in the presence of SLE plasma. However, there was no difference in the [3H]TdR response or the percentage of cells in S, G2, and M phases when T lymphocytes from the hypocomplementemic patients were stimulated on either autologous or normal allogeneic monocyte monolayers. Likewise, normal lymphocytes incorporated similar amounts of [3H]TdR and had similar percentages of cells in S, G2, and M phases whether their T lymphocytes were stimulated on autologous or SLE monocyte monolayers. Highly purified subpopulations of B and T lymphocytes were obtained by density sedimentation or Fenwal Leuko-Pak passage of lymphocyte populations. The response to PHA by lymphocytes from the hypocomplementemic lupus patients could be seen to involve at least two abnormalities. One, in reference to normal lymphocytes, SLE T lymphocytes plus monocytes had an impaired response; two, SLE B lymphocytes plus SLE T lymphocytes plus SLE monocytes had an impaired response. Two patients in the hypocomplementemic group were treated with steroids. 5 days after steroid treatment was initiated, the percentage of cells in S, G2, and M phases and the [3H]TdR response of PHA-stimulated lymphocytes returned to normal. The normalization of the [3H]TdR response was explained both by a return of purified T cells plus monocytes, purified B cells plus monocytes, and whole lymphocyte populations to normal responsiveness. These studies suggest that a steroid-correctable defect exists in T and B lymphocytes in SLE.
Authors
Peter D. Utsinger, William J. Yount
Citation Information: J Clin Invest. 1977;60(3):665-674. https://doi.org/10.1172/JCI108818.
Abstract
The small intestine is capable of taking up peptide nutrients of two or three amino acid residues, but the mechanism of intestinal assimilation of larger oligopeptides has not been established. The amino-oligopeptidase of the intestinal brush border possesses high specificity for oligopeptides having bulky side chains and is a candidate for a crucial role in the overall assimilation of dietary protein.
Authors
Kenneth W. Smithson, Gary M. Gray
Citation Information: J Clin Invest. 1977;60(3):675-682. https://doi.org/10.1172/JCI108819.
Abstract
In earlier studies, methods were developed to raise specific antibodies in rabbits against purified suspensions of mouse or human eosinophils. On administration of antieosinophil serum (AES) to mice, the mature eosinophils in tissues, peripheral blood, and bone marrow were depleted, while the immature eosinophil pool in the bone marrow was observed to proliferate. The current investigations explore the generation of eosinophilopoietic factors during AES-induced eosinophilopenia. Mice received three injections of AES, one every other day. As the peripheral eosinophil counts started to recover after the last AES injection, the serum was collected and transferred to normal animals. Within 2 days the recipients showed an increase in peripheral blood as well as in bone marrow eosinophils. The rise in bone marrow eosinophils was due to newly formed cells as evidenced by increased uptake of [3H]thymidine. The generation of eosinophilopoietic activity was specifically related to depletion of eosinophils but not neutrophils. The eosinophilopoietic activity was: (a) dependent on the volume of serum transferred, (b) lost on dialysis, and (c) largely heat labile. The activity eluted as a low molecular weight substance on G-25 Sephadex and was digested by pronase but not by trypsin. Active fractions collected from G-25 columns were not chemotactic for the eosinophils in vitro. Thus, specific depletion of mature eosinophils generates a low molecular weight peptide which stimulates eosinophilopoiesis in vivo. It is suggested that this substance be named eosinophilopoietin.
Authors
Adel A. F. Mahmoud, Marta K. Stone, Robert W. Kellermeyer
Citation Information: J Clin Invest. 1977;60(3):702-708. https://doi.org/10.1172/JCI108822.
Abstract
The effects of several prostaglandins on lipoprotein lipase activity of mammary gland and adipose tissue and serum triacylglycerol were studied during late pregnancy in rats. Prostaglandins were injected twice daily for 2 days before and once on the day of analysis. In rats pregnant 20 days, prostaglandin F2α (PGF2α) increased the activity of lipoprotein lipase in mammary gland fourfold, reduced the activity in adipose tissue about 60%, and decreased serum concentration of triacylglycerol 50%. PGF2α also reduced serum concentration of progesterone 90% and increased that of prolactin fivefold, but had no effect on serum concentrations of either immuno-reactive insulin or 17β-estradiol. Injections of 13,14-dihydro-15-keto PGF2α, a metabolite of PGF2α, had similar effects in rats pregnant 20 days, whereas prostaglandins E1 and E2 did not. In rats pregnant 16 days, PGF2α did not affect lipoprotein lipase activity in the tissues or the concentration of triacylglycerol and prolactin in serum, although it decreased serum progesterone 80%.
Authors
Peter M. Spooner, Mary M. Garrison, Robert O. Scow
Citation Information: J Clin Invest. 1977;60(3):741-746. https://doi.org/10.1172/JCI108826.
Abstract
Purine-nucleoside phosphorylase (NP) deficiency is associated with severely defective thymus-derived (T)-cell and normally functioning bone marrow-derived (B)-cell immunity. In this study, two unrelated families with a total of three NP deficient members were investigated.
Authors
William R. A. Osborne, Shi-Han Chen, Eloise R. Giblett, W. Douglas Biggar, Arthur A. Ammann, C. Ronald Scott
Citation Information: J Clin Invest. 1977;60(2):284-294. https://doi.org/10.1172/JCI108776.
Abstract
In this study ethanol and certain other short-chain aryl (benzyl and phenethyl) and aliphatic (methyl, propyl, butyl, and amyl) alcohols produced up to 10-fold increases in cyclic AMP (cAMP) concentrations in purified human peripheral blood lymphocytes. Ethanol concentrations as low as 80 mg/dl produced significant elevations in lymphocyte cAMP. Significant but less marked augmentation of cAMP in response to alcohols was observed in human platelets, human granulocytes, and rabbit alveolar macrophages. The mechanism of the alcohol-induced cAMP accumulation is probably secondary to membrane perturbation and consequent activation of adenylate cyclase, because ethanol directly stimulated this enzyme in lymphocyte membrane preparations but had no effect on lymphocyte phosphodiesterase activity.
Authors
John P. Atkinson, Timothy J. Sullivan, James P. Kelly, Charles W. Parker
No posts were found with this tag.
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)