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Biomedical subjects

R Schulz

Publications and source records attributed to R Schulz.

At least 433 records · Page 24Linked to original sources

Atrial natriuretic peptide in lymphoid organs of various species.

1. Evidence for the occurrence of atrial natriuretic peptide (ANP) in various lymphoid organs of different species (rat, mouse, pig, chicken) is provided. 2. ANP precursor material (1-126) as well the physiologically active ANP (99-126), were identified by chromatographic analysis and RIA in extracts of thymus, spleen and lymph nodes of rat, mouse and pig. 3. mRNA coding for ANP was demonstrated both in the thymus and in isolated thymocytes of these species. Furthermore, mRNA for ANP was detected in spleen and lymph nodes (rat and pig). 4. The bursa of Fabricius, thymus glands and spleen of chickens were also shown to express mRNA coding for ANP. 5. These findings provide a firm basis for a link of ANP to the immune system, a novel aspect of possible biological functions of this peptide.

Animals↗

Relationship orientation, quality of prior relationship, and distress among caregivers of Alzheimer's patients.

Communal orientation and closeness of the caregiver-patient relationship were investigated as predictors of distress among caregivers of Alzheimer's patients. Persons high in communal orientation were less depressed than those low in communal orientation. Caregivers reporting a close relationship with the patient before illness onset felt less burdened than those whose relationship had not been close. Communal orientation interacted with closeness when data were analyzed separately for men and women. Among men, being low in communal orientation and having a relatively poor prior relationship were associated with the highest levels of depression, levels that put them at risk for clinical depression. Among women low in communal orientation, higher levels of depression were related to having a close prior relationship with the patient.

Adult↗

On prognostic research in adult neurologic disorders.

This note suggests some changes in variable selection and operationalization for research on prognosis in adult neurologic communicative disorders. The issues raised are relevant to both broad prognostic questions concerning extent of recovery, and focused questions regarding candidacy and treatment efficacy.

Adult↗

A possible linkage of atrial natriuretic peptide to the immune system.

Recent work has suggested the existence of atrial natriuretic peptide (ANP)-like material in lymphoid follicles of the guinea pig intestine. To follow the hypothesis of an association of ANP with the immune system, we now report that the rat thymus, a primary lymphoid organ, is a site of ANP synthesis. This is based on the following experimental evidence: firstly, the material detected corresponds chromatographically with the precursor of ANP. Secondly, the existence of mRNA for ANP in the gland suggests synthesis of the peptide in the gland. Thirdly, immunohistochemical studies locate ANP-like material in cortical thymocytes, predominantly in the subcapsular areas of the thymus. Both ANP-like material and mRNA were present to a larger extent in very young rats. The results communicated here support the notion of a link of ANP with the immune system.

Aging↗

Psychiatric and physical morbidity effects of caregiving.

Existing empirical literature on the prolonged or cumulative consequences of exposure to the stresses of caregiving is reviewed. Specific goals are to identify psychiatric and physical morbidity effects, report the magnitude of those effects, evaluate research and analytic methods used to assess morbidity, and make recommendations for future research. Overall, the literature indicates increases in self-report psychiatric symptomatology and increases in psychiatric illness among most caregivers when compared to population norms or appropriate control groups. However, there is little information on the population prevalence or incidence of clinically significant psychiatric conditions attributable to caregiving. Studies of physical health effects as assessed by self-report, health care utilization, and immune function are less conclusive but, nevertheless, suggest increased vulnerability to physical illness among caregivers. We conclude with a discussion of why morbidity effects are difficult to obtain in caregiver studies and with recommendations for future research.

Attitude to Health↗

Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo.

1. Three analogues of L-arginine were characterized as inhibitors of endothelial nitric oxide (NO) synthase by measuring their effect on the endothelial NO synthase from porcine aortae, on the vascular tone of rings of rat aorta and on the blood pressure of the anaesthetized rat. 2. NG-monomethyl-L-arginine (L-NMMA), N-iminoethyl-L-ornithine (L-NIO) and NG-nitro-L-arginine methyl ester (L-NAME; all at 0.1-100 microM) caused concentration-dependent inhibition of the Ca2(+)-dependent endothelial NO synthase from porcine aortae. 3. L-NMMA, L-NIO and L-NAME caused an endothelium-dependent contraction and an inhibition of the endothelium-dependent relaxation induced by acetylcholine (ACh) in aortic rings. 4. L-NMMA, L-NIO and L-NAME (0.03-300 mg kg-1, i.v.) induced a dose-dependent increase in mean systemic arterial blood pressure accompanied by bradycardia. 5. L-NMMA, L-NIO and L-NAME (100 mg kg-1, i.v.) inhibited significantly the hypotensive responses to ACh and bradykinin. 6. The increase in blood pressure and bradycardia produced by these compounds were reversed by L-arginine (30-100 mg kg-1, i.v.) in a dose-dependent manner. 7. All of these effects were enantiomer specific. 8. These results indicate that L-NMMA, L-NIO and L-NAME are inhibitors of NO synthase in the vascular endothelium and confirm the important role of NO synthesis in the maintenance of vascular tone and blood pressure.

Amino Acid Oxidoreductases↗

Cerebral arteries can generate 5- and 15-hydroxyeicosatetraenoic acid from arachidonic acid.

Products of the lipoxygenase pathway have been implicated in the development of the cerebrovascular spasm that arises after subarachnoid hemorrhage. In particular the hydroperoxyeicosatetranenoic acids (HPETEs), which are unstable and break down rapidly to the corresponding 5-hydroxy acids (HETEs), are vasoconstrictor agents that mimic some aspects of cerebrovascular spasm. It is not, however, well established whether segments of cerebral artery can manufacture these products. We have studied the lipoxygenase product profile of cerebral arteries stimulated with arachidonic acid. Rings of bovine cerebral arteries were incubated in Krebs solution containing arachidonic acid. The lipoxygenase products were studied using high performance liquid chromatography. The largest peaks had the retention times of 5- and 15-HETEs, and the identity of these peaks was confirmed using specific radioimmunoassays. Stimulation with arachidonic acid resulted in a time- and dose-dependent increase in the formation of both HETEs, with 15-HETE being most abundant. The release of both HETEs was markedly reduced in the presence of AA-861, an inhibitor of lipoxygenase, but not with the cyclooxygenase inhibitor indomethacin. These data are thus consistent with our previous suggestion that the contractile activity of arachidonic acid in cerebral arteries arises, at least in part, from HPETE formation and with a possible role for these compounds in cerebral vasospasm.

Animals↗

Changes of left ventricular diastolic function in exercising dogs without and with ischemia.

Left ventricular (LV) diastolic function in the absence and presence of regional ischemia was examined in eight conscious dogs chronically instrumented with ultrasonic devices for measuring LV wall thickness and volume. During treadmill exercise, ischemia was induced (hydraulic occluder) to produce less than 10% systolic wall thickening in the ischemic zone. LV filling was assessed by the peak filling rate (PFR), mean filling rates in the first and second halves of filling (mFR1 and mFR2), an early filling index from mitral valve opening to minimal diastolic pressure (PDm), and the percentage of atrial filling. Also, LV relaxation (tau) and wall thinning rates during isovolumetric relaxation and the first and second halves of the filling phase were assessed. During control exercise without ischemia, PDm decreased by 2.61 mm Hg (p less than 0.05) to -1.1 mm Hg and there was a downward shift of the entire LV diastolic pressure-volume (P-V) curve. The LV relaxation rate, PFR, mFR1, and mFR2 were enhanced. Early filling was increased by 116%, the percentage of atrial filling by 118%, and overall diastolic filling by 23% despite a 63% decrease in the filling period. During ischemic exercise, systolic function was depressed compared with the resting state, PDm increased by 4.84 mm Hg (p less than 0.005) associated with a pronounced rightward and upward shift of the early portion of the P-V curve. LV relaxation rate, PFR, and mFR1 were reduced, the early filling index fell sharply by 62% but percentage of atrial filling was unchanged, while overall diastolic filling decreased by 30%. The thinning rate of the control wall was enhanced, whereas that of ischemic wall was depressed. Multiple factors contributed to the markedly impaired early and overall diastolic LV filling during ischemia, including impaired systolic function, reduced relaxation rate, nonuniformity of wall motion, an upward shift of the early diastolic P-V curve, and absence of a compensatory increase in late diastolic filling.

Animals↗

Atrial natriuretic peptide is synthesized in the human thymus.

Various neuropeptides have recently been isolated from the thymus, suggesting an interaction between the neuroendocrine and immune systems. We report here that the human thymus synthesizes a further peptide hormone, namely atrial natriuretic peptide (ANP). This is documented by the following findings. ANP and its prohormone were detected in thymic tissue by chromatographic analysis as well as by RIA; the thymus gland and, in particular thymocytes, contain mRNA coding for ANP. Since ANP is common to the brain and the immune system, these data support the notion of the existence of a neuroendocrine-immune axis.

Atrial Natriuretic Factor↗

Dexamethasone action on rat thymic atrial natriuretic peptide.

The rat thymus gland expresses the ANP gene and synthesizes the ANP-precursor, suggesting a role for this peptide within the immune system. This study provides further evidence for this notion, as expression of ANP mRNA in the thymus is altered in response to administration of the glucocorticoid dexamethasone to rats (1.5 mg/kg). This drug causes involution of the thymic gland and at day 4 after steroid exposure a striking increase (up to 30 fold) in mRNA coding for ANP was observed. The increase of the ANP precursor was found to be 4-fold as compared to saline treated controls. During regeneration of the thymus the mRNA and precursor levels normalize, reaching control values the day 18 after dexamethasone. The strong stimulation of the thymus ANP system subsequent to the glucocorticoid may suggest a critical function of this peptide in mechanisms leading to cellular depletion or during the regeneration of the gland after exposure to the steroid.

Animals↗

[Detection of dexamethasone in horses].

Due to their marked antiinflammatory effect, synthetic corticosteroids are used to mask illness, especially lameness in horses. The detection of these drugs in equine body fluids requires accurate methods, particularly where misuse of corticosteroids is suspected. Gas chromatography/mass spectrometry (GC/MS) is well established as a reliable technique for the identification of drugs in biological fluids. Using GC/MS, we determined dexamethasone levels in horse urine and serum after intravenous application of a therapeutic dose. Dexamethasone was detectable, in serum for up to six hours, and in urine for up to 32 hours, after its administration. These findings indicate that serum measurements are unreliable for the detection of corticosteroid abuse, and demonstrate urine to be a more suitable body fluid for investigation. Nevertheless, it should be emphasized that, regardless of the technique employed, the clinical effects of dexamethasone last longer than 32 hours; thus, failure to detect dexamethasone does not disprove corticosteroid abuse.

Animals↗

Development of an ELISA for the detection and determination of contaminating proteins in recombinant DNA derived human erythropoietin.

An enzyme linked immunosorbent assay (ELISA) has been developed for the quantitative determination of the most probable contaminating proteins (MCP) of recombinant human Erythropoietin produced in the mouse fibroblast cell line C-127. The developed ELISA is a double polyclonal sandwich type immunoassay, which allows a quantitation of the MCPs in the range of parts per million. The polyclonal antibody, used for both coat and conjugate in this ELISA, was demonstrated to be reactive with the reference MCPs (a collection of the most probable protein contaminants) by immunoblot analysis and immunoabsorption of radiolabeled MCPs. Affinity purification of this antibody preparation using the immobilized MCPs resulted in an assay with higher signal-to-noise ratio. The assay was demonstrated to be very specific for the MCPs obtained from the rhu EPO purification process. Since the purification of each recombinant DNA derived protein expressed in mammalian cells requires its own unique process, no generic assay for contaminating proteins can be developed. There are only a few common criteria for the development of such multi-antigen ELISA, which will be discussed in this paper.

Animals↗

Physician adaptation to health maintenance organizations and implications for management.

The growth of health maintenance organizations (HMOs) and other forms of managed care presents a challenge to traditional patterns of private practice. In Dane County, Wisconsin (Madison Metropolitan Area), the proportion of the population enrolled in closed-panel HMOs increased dramatically, from 10 percent in 1983 to over 40 percent by 1986. This study surveyed 850 practicing physicians regarding their expectations before, and experiences after this rapid change to competitive HMOs. Although most physicians expected a loss of earnings and lower-quality care, the majority reported that neither declined. However, most physicians expected and reported a decline in their autonomy. Primary care physicians were most supportive of the change to HMOs. The implications of these findings for management practices are discussed.

Adaptation, Psychological↗

Allogeneic mixed lymphocyte reactions during a second round of ontogeny: normal accessory cells did not restore defective interleukin-2 (IL-2) synthesis in T cells but induced responsiveness to exogeneous IL-2.

The T-cell-accessory-cell interaction in mixed lymphocyte cultures was investigated in 25 patients following autologous bone marrow transplantation (ABMT) using autologous bone marrow treated in vitro with the cyclophosphamide derivative ASTA Z 7557. In a previous study using the same group of patients, T cells failed to synthesize interleukin-2 (IL-2) and proliferate in response to CD3- and CD2-mediated stimuli even in the presence of exogenous IL-2. To investigate whether this defect in IL-2 synthesis and proliferation was caused by defective cell-to-cell interactions, we analyzed mixed lymphocyte reactions (MLR) using T cells and irradiated non-T cells. When normal T cells from 10 different healthy subjects were challenged with allogeneic normal non-T cells, IL-2 production and proliferation were observed. In contrast, when normal T cells were cultured with non-T cells derived from patients found between 20 and 330 days after ABMT, no IL-2 secretion and no proliferative responses could be seen. The addition of lymphokines such as interleukin-1 (IL-1), interleukin-3 (IL-3), tumor necrosis factor (TNF), granulocyte-macrophage colony stimulating factor (GM-CSF), and interferon-gamma (IFN-y) did not improve the reactions. Furthermore, when patients' T cells were incubated with normal, irradiated non-T cells, defective IL-2 synthesis or proliferative response was obtained. However, when IL-2 was added to these cultures, an improvement in proliferative reactions was observed. Taken together, these new data provide additional evidence that T cells early in ontogeny possessed an intrinsic defect in IL-2 synthesis and that physical cell-to-cell contact between patients' T cells and allogeneic accessory cells induced functional responsiveness to exogeneous IL-2.

Antigen-Presenting Cells↗

T-cell ontogeny after autologous bone marrow transplantation: failure to synthesize interleukin-2 (IL-2) and lack of CD2- and CD3-mediated proliferation by both CD4- and CD8+ cells even in the presence of exogeneous IL-2.

T cells generated during a second round of ontogeny after autologous bone marrow transplantation (ABMT) represent a unique model of early T-cell ontogeny in an autologous situation. Since grafted bone marrows were pretreated in vitro with the cyclophosphamide derivative ASTA Z 7557, circulating T cells had to be regenerated from reinfused hematopoietic progenitor cells. The T-cell population derived from 25 patients post-ABMT was phenotypically characterized: an increase in CD8+ cells, a low percentage of CD4+ cells, and a median of 12% CD56+ (NKH1+) cells were found. When the T cells were stimulated with phytohemagglutinin (PHA) and phorbol myristate acetate (PMA), defective interleukin-2 (IL-2) secretion was observed. In addition, proliferative responses of the T cells after activation through the antigen-receptor-dependent CD3 pathway, through the CD2 dependent alternative T-cell pathway, and by the lectin PHA were investigated. Despite the presence of CD2, CD3, alpha/beta chains of the T-cell receptor, and CD25+ IL-2 surface receptors, abnormal proliferative responses were obtained even in the presence of exogeneous IL-2. In experiments where the T-cell population was separated into CD4+ cells and CD8+ cells, both the CD4- and CD8+ subsets were unable to respond to activating and proliferating signals. Thus, T cells at early stages of ontogeny not only possess an intrinsic defect in IL-2 synthesis but, in addition, were unable to express functional IL-2 receptors in response to mitogenic stimuli.

Antigens, Differentiation, T-Lymphocyte↗

Quantitative determination of kinins released by trypsin using enzyme-linked immunosorbent assay (ELISA) and identification by high-performance liquid chromatography (HPLC).

Rapid ELISA and HPLC procedures were developed for quantitation and identification of various natural kinins. Antibradykinin mouse monoclonal antibodies were used to determine kinin levels in the range of 20-200 ng. Bradykinin coupled to bovine serum albumin was used to coat the plates in a 3- to 4-hr ELISA. Synthetic kinin standards isoleucine-seryl-bradykinin (Ileu-Ser-BK), methionyl-lysyl-bradykinin (Met-Lys-BK), tyrosine-bradykinin (Tyr-BK) and bradykinin (BK) yielded almost identical curves with a mixture of A5 and D9 monoclonal antibodies. [Tyr5]-BK, [Tyr8]-BK and des-arginine9 bradykinin (des-Arg9-BK) showed negligible amounts of cross-reactivity. ELISA-compatible trypsin digestion developed for release of kinins from plasma of normal humans, rats and turpentine-treated rats gave values of 3.2, 6.9 and 70 micrograms/ml plasma, respectively. High performance liquid chromatography methods were developed for complete resolution of kinins on a C-18 reversed phase mu-Bondapak column before and after derivatization with phenyl isothiocyanate (PITC). The simple PITC derivatization procedure yielded good quantitation above 20 pmol. The ELISA and HPLC methods were used in a complementary fashion to assay and identify kinins in biological fluids as well as during the course of kininogen purification.

Animals↗