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Objective: To examine the relation of patient beliefs about medication usage and adherence to zidovudine (ZDV) therapy in persons with AIDS.Design: Face-to-face interviews were used to determine attitudes of persons with AIDS toward ZDV and other prescribed medications, history of ZDV usage, and sociodemographics.Setting: A public hospital infectious disease clinic, an AIDS day care program, and an inpatient unit in a voluntary hospital where care was provided cooperatively by staff and an informal-care partner.Patients/participants: One hundred forty-one people with the acquired immunodeficiency syndrome agreed to be reinterviewed as part of a longitudinal, New York City-based study examining outcomes related to quality of life. Initial recruitment procedures were to approach all active AIDS patients at each of the three sites between January and July of 1992: reinterviews, which were conducted an average of 6 months later, occurred from mid-1992 through May of 1993.Measurements and Main Results: The Zidovudine Drug Attitude Inventory was used to assess subjective feelings and attitudes concerning ZDV and prescribed medications in general. Respondents were grouped into five categories on the basis of their ZDV usage history: (1) "short-term" users (i.e., those who had been taking ZDV for 25 months or less); (2) "long-term" users (i.e., those who had been taking ZDV for more than 25 months); (3) self-terminated users; (4) doctor-terminated users; and (5) never users. Long-term users were likely to view ZDV as an illness prophylactic. In contrast, self-terminated users and never users were most likely to believe that ZDV caused adverse side effects and that medicine need not be taken as prescribed.Conclusions: Patients' beliefs about ZDV were significantly associated with adherence-related behavior. In particular, those who had self-terminated ZDV treatment believed that taking the drug was harmful, were skeptical of its ability to prevent illness, and felt that physician's directives about medication usage in general could be disregarded. These findings highlight the importance of educating patients about ZDV and of establishing regular patient-clinician exchanges concerning patient's experience with and beliefs concerning ZDV. [ABSTRACT FROM AUTHOR]

The efficacy of T cell-based immunotherapies is limited by immunosuppressive pressures in the tumor microenvironment. Here we show a predominant role for the interaction between BTLA on effector T cells and HVEM (TNFRSF14) on immunosuppressive tumor microenvironment cells, namely regulatory T cells. High BTLA expression in chimeric antigen receptor (CAR) T cells correlated with poor clinical response to treatment. Therefore, we deleted BTLA in CAR T cells and show improved tumor control and persistence in models of lymphoma and solid malignancies. Mechanistically, BTLA inhibits CAR T cells via recruitment of tyrosine phosphatases SHP-1 and SHP-2, upon trans engagement with HVEM. BTLA knockout thus promotes CAR signaling and subsequently enhances effector function. Overall, these data indicate that the BTLA-HVEM axis is a crucial immune checkpoint in CAR T cell immunotherapy and warrants the use of strategies to overcome this barrier., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Airway and alveolar inflammation have been described in asthma. Prolonged inflammation may lead to airway remodeling, which can result in physiologic abnormalities. Elderly lifetime nonsmokers are an ideal population in which to examine the consequences of longstanding asthma. To test the hypothesis that airflow limitation and hyperinflation are associated with the duration of asthma, we evaluated airflow and lung volumes in a cohort of elderly asthmatic individuals. All subjects were > 60 yr of age and were lifetime nonsmokers (n = 75). Patients with asthma of long duration (LDA; n = 38) had asthma for >/= 26 yr (median = 40.0 yr); patients with asthma of short duration (SDA; n = 37) had asthma for < 26 yr (median = 9 yr). Patients with LDA had a significantly lower FEV(1)% predicted than did those with SDA (59.5 +/- 2.6% versus 73.8 +/- 3.1% [mean +/- SEM], respectively; p < 0.007). Regression analysis demonstrated that duration of asthma was inversely associated with FEV(1)% predicted (r = 0.264, p < 0.03). After bronchodilator administration, the patients with LDA continued to show airflow obstruction (FEV(1)% predicted = 65.4 +/- 2.9). Only 18% of patients with LDA attained a normal postbronchodilator FEV(1), whereas 50% of those with SDA were able to do so (p < 0.003). The FRC% predicted was significantly higher in subjects with LDA than in those with SDA (142.9 +/- 5.6 versus 124.1 +/- 4.4, respectively, p < 0.01). Multiple regression analysis revealed an association between FRC and duration of asthma that was independent of the degree of airflow limitation. These data suggest that the duration of asthma is associated with the degree of airflow limitation and hyperinflation. Moreover, these abnormalities can become irreversible over time, and may reflect distal airway and/or parenchymal changes as well as proximal airway remodeling.

Objective: To examine the relation of patient beliefs about medication usage and adherence to zidovudine (ZDV) therapy in persons with AIDS., Design: Face-to-face interviews were used to determine attitudes of persons with AIDS toward ZDV and other prescribed medications, history of ZDV usage, and sociodemographics., Setting: A public hospital infectious disease clinic, an AIDS day care program, and an inpatient unit in a voluntary hospital where care was provided cooperatively by staff and an informal-care partner., Patients/participants: One hundred forty-one people with the acquired immunodeficiency syndrome agreed to be reinterviewed as part of a longitudinal, New York City-based study examining outcomes related to quality of life. Initial recruitment procedures were to approach all active AIDS patients at each of the three sites between January and July of 1992: reinterviews, which were conducted an average of 6 months later, occurred from mid-1992 through May of 1993., Measurements and Main Results: The Zidovudine Drug Attitude Inventory was used to assess subjective feelings and attitudes concerning ZDV and prescribed medications in general. Respondents were grouped into five categories on the basis of their ZDV usage history: (1) "short-term" users (i.e., those who had been taking ZDV for 25 months or less); (2) "long-term" users (i.e., those who had been taking ZDV for more than 25 months); (3) self-terminated users; (4) doctor-terminated users; and (5) never users. Long-term users were likely to view ZDV as an illness prophylactic. In contrast, self-terminated users and never users were most likely to believe that ZDV caused adverse side effects and that medicine need not be taken as prescribed., Conclusions: Patients' beliefs about ZDV were significantly associated with adherence-related behavior. In particular, those who had self-terminated ZDV treatment believed that taking the drug was harmful, were skeptical of its ability to prevent illness, and felt that physician's directives about medication usage in general could be disregarded. These findings highlight the importance of educating patients about ZDV and of establishing regular patient-clinician exchanges concerning patient's experience with and beliefs concerning ZDV.

We evaluated the effects of maternal asthma on specific parameters of family function including the children's school attendance and mother's performance of basic parenting tasks. A case-controlled study of mothers with asthma (MA; n = 24) with children under the age of 13 and matched mothers without asthma (CM; n = 27) was performed. Children of mothers with asthma had a significantly impaired ability to attend school compared to children of control mothers (odds ratio = 15, 95% CI). Twenty-two percent of MA reported that their asthma caused their children to miss school at least once per month. In addition, 27% of MA reported that their children were regularly late for school because of the mother's asthma. Only 5% of the control mothers reported that their health caused their children to miss school, and none reported lateness. Asthma also impaired the ability of the MA to perform basic parenting tasks such as dressing children and preparing meals for children. These adverse effects of parental asthma on children's school attendance and parenting represent previously unappreciated indirect costs of asthma and may have immediate as well as future consequences.

A variety of normal human ovarian tissues as well as benign and malignant human ovarian neoplasms have been examined in vitro for the presence of gonadotropin binding sites and gonadotropin-stimulable cAMP production, in order to determine whether gonadotropic hormones have an effect on ovarian tumors. Binding of either FSH or hCG, or both, was demonstrated in several tumors from each of the histologic subgroups of primary ovarian tumors, including epithelial, sex cord-stromal, and germ cell types. Cyclic AMP stimulation was found in one tumor of sex cord-stromal origin, in two of epithelial origin, in two of germ cell origin, and in one tumor-like condition, pregnancy luteoma. Additional biochemical studies are needed to characterize receptor sites and to relate them to histologic features, growth behavior in vivo, and serum gonadotropin levels.

A new radioimmunoassay for human procollagen showed that the sera of 46 of 50 untreated patients with Paget's disease of bone contained increased concentrations of procollagen protein as compared to normal adults. After therapy with disodium etidronate, all the elevated serum procollagen concentrations decreased significantly, falling to normal levels in 33 of 40 patients. The procollagen levels before and after treatment were coordinate with the values for urinary total hydroxyproline and serum alkaline phosphatase activity. The data show that the radioimmunoassay for procollagen is a dependable and useful adjunct to the study of Paget's disease of bone.

A case of a progressive virilizing solid granulosa-theca cell tumor producing high testosterone levels that were suppressed to normal by a course of oral contraceptives is presented. In vitro studies demonstrated significant specific follicle-stimulating hormone (FSH) receptors on the tumor. The studies of the biological response to gonadotropins in terms of cyclic AMP generation also indicate that the tumor is responsive to gonadotropic hormones in vitro, and are consistent with the in vivo clinical response. A discussion of the role of gonadotropins in the etiology or maintenance of ovarian tumors is also presented.

A nonluteinized granulosa cell ovarian tumor and a purely luteinized ovarian tumor, induced by gonadotropin stimulation in mice, were studied ultrastructurally to obtain evidence concerning the possible origin of these tumors, whether from granulosa cells only or from granulosa and theca. Evidence including the presence of cells sharing features of both nonluteinized and luteinized cells, the presence of desmosomes and other junctional complexes in both cell types, and the presence of partially extracted lipid droplets in the luteinized cells suggests that the luteinized cells represent granulosa-lutein cells rather than theca-lutein cells. These findings are consistent with the concept that these tumors represent a spectrum of differentiation from nonluteinized granulosa cells to luteinized granulosa cells. The lack of theca and theca-lutein cells in both tumors implies that theca cells are not involved as progenitor cells.

Gonadotropic hormones are required for the induction and maintenance of tumors arising in ovaries that have been transplanted to the spleens of gonadectomized mice. The characteristics of gonadotropin receptors for human chorionic gonadotropin (HCG)-luteinizing hormone on cells from these tumors of varying size, age, and morphology have been determined. The specific binding of 125I-labeled HCG to cells obtained by collagenase digestion, 15 to 65 weeks postimplantation from granulosa cell or luteinized cell, or mixed granulosa-luteal tumors was analyzed by Scatchard plot. Neither the size, weight, duration of implantation, nor histological morphology affected the receptor-binding affinity [equilibrium dissociation constant (Kd), 6 X 10(-10) M], and, presumably, the receptor is qualitatively similar. In contrast, the number of HCG receptors per cell increased 17-fold and was related to the degree of morphological luteinization of the tumor. HCG-sensitive adenyl cyclase was also demonstrated and compared to HCG binding in a highly luteinized tumor.

Human placental fragments concentrate 86Rb 10--20-fold during a two-hour incubation period. Inhibition of ouabain is dose-dependent, reaching 90 + per cent at a concentration of 5 x 10(-5) M. The clearance index of 86Rb across the perfused human placenta is 0.34 +/- 0.08, comparing to previously reported indices for Na22 and Cl36 of 0.28 and 0.41, respectively. Ouabain in concentrations up to 5 x 10(-5) M had no detectable effect on transfer across the placenta. The clearance index of ouabain is low, averaging 0.07 in 3 experiments. 3H-ouabain is not detectably bound to albumin or placental homogenate.

It is estimated that 66% of patients with Paget's disease have involvement of the pelvis and 46% of the proximal femur. Therefore, it is not unexpected that hip pain is one of the major presenting complaints. Analysis of the radiographs of 25 hips with one or more articular sufaces involved by Paget's disease demonstrated narrowing in 24. Unlike the findings in primary degenerative joint disease, the majority of cases had a radiographic pattern characterized by uniform narrowing of the articular cartilage and minimal hypertrophic changes. Pathologic correlation was obtained from specimens of four patients who underwent total hip replacements. The pathogenesis of arthritic changes associated with osteitis deformans is not established. The evidence presented suggest that cartilagenous narrowing results from a disturbance in endochondral bone formation related to the hyperemia of Paget's disease. Secondary deformities of bone produce further derangement of joint mechanics. The secondary degenerative changes which ensue differ mechanically, and therefore radiographically, from primary degenerative joint disease.

In order to evaluate and quantitate the therapeutic efficacy of disodium etridonate (EHDP) in the treatment of Paget's disease, a prospective double-blind study was instituted. Subjects received either placebo, low-dose EHDP, or high-dose EHDP and were evaluated prior to therapy and 6 months later. Bone scans were performed with 99mTc or 18F and radioisotopic uptake studies were conducted. The results were correlated with clinical improvement, biochemical parameters, and radiographic skeletal surveys, and indicate that the radioisotopic uptake studies are both a sensitive and reproducible means of evaluating the degree of response to EHDP.

The unique combination of male hypogonadism with hypoparathyroidism, hypoadrenalism, hypothyroidism, diabetes mellitus, and alopecia totalis has been documented in a male patient who has been followed over the past 28 years. In this patient, first seen at the age of six for hypoparathyroidism alone, repeated clinical and laboratory endocrine evaluation detected the sequential development of the additional endocrine deficiencies. The presence of abnormal serum antibodies is consistent with an atuoimmune pathogenesis of this syndrome.

The binding of both human chorionic gonadotropin (hCG) and human luteinizing hormone (hLH) to a homogeneous population of isolated intact granulosa cells from increasingly mature porcine ovaan follicles has been studied. The number of receptor sites per granulosa cell increases 35-fold as the follicle enlarges, although cell size remains constant. This may explain the increased biologic responsiveness to gonadotropin of mature cells from large follicles. The affinity for both hormones, as determined by equilibrium dissociation constants, is high, and does not appear to change significantly as the cells mature. Comparison of dissociation constants, numbers of binding sites, and competitive inhibition between hCH and hLH, indicates that these two hormones probably interact with the same receptor on the granulosa cells.

Several patients with Paget's disease have been reported to have monoclonal IgM proteins in their serum. We have systematically studied 26 patients with Paget's disease severe enough to require diphosphonate therapy. Five of these patients were found to have isolated elevations of serum IgM which were well outside the normal range for their age, sex and race. An additional patient had elevations of both IgG and IgM. These patients seem to represent a subset of Pagetics. They do not differ from the remainder of the group with respect to severity or extent of disease, response to therapy, presence of intercurrent disease or age. They do have a different male to female ratio. These observations suggest that some patients with Paget's disease may have disordered immune regulation or that they may be undergoing a primary response to an agent involved in the aetiology or pathogenesis of the disease.

Clearance indices (clearance of experimental material: clearance of antipyrine, CI) across the perfused human placenta were determined for urea, sodium, and chloride. The selected materials are of relatively small molecular weight and are water soluble. Clearance of urea was determined under conditions of net transfer and of exchange and no difference was detected. Sodium and chloride clearances were measured as exchange rates. The CI were: urea, 0.32 and 0.38 toward fetus and mother, respectively); sodium, 0.28; and chloride, 0.41 (measured toward the fetus). Recalculation of data as the diffusion limitation (LD) facilitated comparison with data in the literature on the monkey, rabbit, and sheep. LD for urea was comparable among the four species whereas the sheep placenta differed, sharply limiting the diffusion of sodium and chloride. The discrepancy in the sheep between urea and sodium indicates that the low transfer rate of the latter cannot be explained by the "thickness" of the syndesmochorial placenta, as is often stated. Inferences concerning nitrogen metabolism in the fetus have been derived by others from data on transplacental urea gradients and urea clearance. Available data in the human are incomplete but are consistent with amino acids providing approximately 10% of fetal energy needs, with glucose serving as the predominant substrate.

Selective release of inflammatory materials from leukocyte lysosomes is reduced by compounds which increase cyclic 3',5'-adenosine monophosphate (cAMP) levels in suspensions of human leukocytes and is augmented by agents which increase cyclic 3',5'-guanosine monophosphate (cGMP) levels in these cell suspensions. Lysosomal enzymes are released in the absence of phagocytosis when cytochalasin B (5 mug/ml) converts polymorphonuclear leukocytes (PMN) to secretory cells: lysosomes merge directly with the plasma membrane upon encounter of PMN with zymosan, and cells selectively extrude substantial proportions of lysosomal, but not cytoplasmic enzymes. beta-Adrenergic stimulation of human leukocytes produced a dose-related reduction in beta-glucuronidase release (blocked by 10(-6) M propranolol) whereas alpha-adrenergic stimulation (phenylephrine plus propranolol) was ineffective. In contrast, the cholinergic agonist carbamylcholine chloride enhanced enzyme secretion, an effect blocked by 10(-6) M atropine. Incubation of cells with exogenous cAMP or with agents that increase endogenous cAMP levels (prostaglandin E1, histamine, isoproterenol, and cholera enterotoxin) reduced extrusion of lysosomal enzymes; in contrast, exogenous cGMP and carbamylcholine chloride (which increases endogenous cGMP levels), increased beta-glucuronidase release. Whereas colchicine (5 x 10(-4) M), a drug which impairs microtubule integrity, reduced selective enzyme release, deuterium oxide, which favors microtubule assembly, enhanced selective release of lyosomal enzymes. The data suggest that granule movement and acid hydrolase release from leukocyte lysosomes requires intact microtubules and may be modulated by adrenergic and cholinergic agents which appear to provoke changes in concentrations of cyclic nucleotides.