Testosterone and testosterone precursors in the spermatic vein and in the testicular tissue of old men. Reduced oxygen supply may explain the relative increase of testicular progesterone and 17 alpha-hydroxyprogesterone content and production in old age

Testosterone and the testosterone precursors pregnenolone, progesterone, 17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolone, androstenedione, androstenediol and dehydroepiandrosterone were measured in the spermatic vein plasma and in the testicular tissue of young and old men. Testosterone and its precursors decreased in the testicular tissue of old men. However, progesterone and 17 alpha-hydroxyprogesterone increased in relation to testosterone in the testicular tissue and in the spermatic vein of old men. It is assumed that these age-dependent changes are caused by an impaired oxygen supply of the ageing testes. This hypothesis is supported by the observation that the same changes in steroid pattern seen in old age can be observed under reduced oxygen supply in in vitro incubation experiments with testicular tissue.     

Chloramphenicol antibody causing interference in antibody detection and identification tests

Investigation of the serum of three patients with positive antibody detection tests demonstrated the cause in each to be an antibody against chloramphenicol, a bacteriostatic agent used in commercial red blood cell reagents. Washing of these red cells prior to use prevented agglutination. All three examples of anti-chloramphenicol antibody were IgM and were in low titer when tested at room temperature and 37 C in saline. Two of the antibodies bound complement. The possibility of an antibody to an ingredient of the commercial preservative solution should be considered if problems are encountered in tests with unwashed commercial red blood cell reagents.     

Inhibition of feline collateral vessel development following experimental thrombolic occlusion

We compared development of feline hindlimb collateral circulation after acute occlusion of the terminal aorta by ligation, thrombus formation, and formation of a "closed" aortic loop containing thromboplastin. Collateral circulation development was assessed by aortograms, scintillation scans, neurological signs following occlusion, measurement of hindlimb muscle blood flow, and forelimb and hindlimb temperature. In cats in which aortic occlusion was the result of ligation or thromboplastin in the aortic loop, paralysis was not evident. Aortograms and scintillation scans indicated hindlimb blood flow. Both muscle temperature and blood flow data indicated that the return of blood flow was rapid. The 5th lumbar artery appears to be the origin of the collateral vessels. The mid-zone component is a dorsal and ventral vertebral route and an epaxial muscle route. The reentry components are the 6th or 7th lumbar arteries. The collateral vessels arise from preexisting collateral vessels. Of those cats in which aortic occlusion was the result of a thrombus, all exhibited paralysis. Aortograms, scintillation scans, muscle temperature, and hindlimb blood flow data indicated reduced hindlimb blood flow. The results suggest that the thrombus has an inhibitory effect on the development of collateral circulation.     

Attitudes toward aging and towards the needs of older people

In order to explore the underlying dimensionality of beliefs about aging, two sets of opinion statements (one dealing with general attitudes toward aging and the other with programmatic issues) were factor analyzed for two age groups: persons under 60 (N = 290) and persons 60 and older (N = 181). For the first set of social-psychological belief statements, a common factor structure was found for the two age groups. For the second set of programmatic statements, there was some communality between age groups, but most of the items loading on the factors tended to be age-specific. The belief structure of the older group was generally more complex and variegated than was the case with the younger group. Except where the items were personal relevance, positive and negative items tended to load on separate, unipolar factors.     

Synovial-type (group II) phospholipase A2 human seminal plasma

Phospholipase A2 (PLA2) was analysed in seminal plasma of fertile, subfertile, and vasectomized men as well as in prostatic secretion and tissue. Immunological cross-reactivity was observed between synovial-type PLA2 antiserum and the enzyme present in seminal plasma. There was a highly significant correlation between the concentration of the synovial-type PLA2, as measured by a time-resolved fluoroimmunoassay and the catalytic activity of the PLA2. The results show that the PLA2 content in human seminal plasma is very high (approximately 1000 times of that present in blood plasma) and that the enzyme belongs to the synovial-type group II phospholipase A2. The results also indicate that the enzyme is secreted by the prostate.     

Identification and target-size analysis of the leukotriene D4 receptor in the human THP-1 cell line

The human acute monocytic leukemia cell line THP-1 has been identified, by radioligand binding, as expressing the leukotriene D4 receptor at a high level (4000 binding sites per cell), without the need for further cell differentiation. [3H]Leukotriene D4-specific binding to THP-1 cell membranes was of high affinity (KD = 0.47 nM) and saturable, enhanced by divalent cations but inhibited by both monovalent cations and non-hydrolyzable GTP analogs. The cysteinyl leukotrienes competed for [3H]leukotriene D4-specific binding with the following rank order of potency: leukotriene D4 > leukotriene E4 > leukotriene C4. In addition, leukotriene D4-receptor antagonists from two structural classes, the quinolines MK-571 and L-697,008, and the indole ICI 204,219, displayed nanomolar potency in [3H]leukotriene D4 competition assays. These data show that [3H]leukotriene D4-specific binding to THP-1 cell membranes fulfils the criteria for binding to a leukotriene D4 receptor regulated through interaction with a G protein. Several novel features of the THP-1 leukotriene D4 receptor were investigated. Culture of THP-1 cells in the presence of tunicamycin, an inhibitor of N-glycosylation, resulted in a 6-fold decrease in the number of detectable [3H]leukotriene D4-specific binding sites. Target-size analysis by radiation inactivation estimated a molecular mass of 65 kDa for the [3H]leukotriene D4 specific binding site(s) present in THP-1 cell membranes. Together, these results suggest that the human THP-1 cell leukotriene D4 receptor is a glycosylated protein with a molecular mass of approx. 65 kDa within the membrane environment.     

Effect of immunomodulators in the hu-PBL-SCID mouse model

The effects of two immunomodulators were investigated in severe combined immunodeficient mice reconstituted with human peripheral blood lymphocytes (hu-PBL-SCID mice). Both immunomodulators, maleic anhydride divinyl ether (MVE-2) and 4-imino-1,3-diazobicyclo-(3.1.0)-hexan-2- one (imexon), have been previously studied by us in retrovirus-infected mice. To determine the effects of these compounds as they may function in humans, 24 SCID mice were each reconstituted with 20 x 10(6) ficoll-purified lymphocytes from a single donor. Five weeks after reconstitution, the mice received 16 mg/kg/day of MVE-2 intraperitoneally (i.p.) on days 0, 7, and 14 or 110 mg/kg/day of imexon i.p. daily for 14 days. Spleens were removed and splenocytes labeled with monoclonal antibodies for T- and B-cell enumeration as determined by flow cytometry 24 h after final treatment. Imexon-treated mice demonstrated a slight increase in total T cells and T cell subsets compared to control mice. T helper/T suppressor cell ratios in imexon-treated mice were brought to a normal 3:2 ratio compared to placebo-treated mice. Human immunoglobulin levels were markedly increased in imexon-treated mice. MVE-2-treated hu-PBL-SCID mice had significantly reduced numbers of total T cells compared to controls. The T-cell population results using human cells in SCID mice were similar to the effects of these immunomodulators on murine cells in immunologically competent mice.     

Noninvasive assessment of the direct action of oral nifedipine and nicardipine on left ventricular contractile state in patients with systemic hypertension: importance of reflex sympathetic responses

BACKGROUND: Alveolar macrophages from patients with sarcoidosis were analyzed for their ability to secrete tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1-beta), and interleukin-6 (IL-6). RESULTS: Constitutive release of all three monokines in these patients was concomitantly increased in the active state of disease in comparison with inactive sarcoidosis or healthy control subjects. Alveolar macrophages from patients with inactive sarcoidosis compared with cells from healthy subjects showed increased spontaneous secretion of TNF-alpha and IL-6 only, whereas the constitutive release of IL-1-beta was similar as in healthy volunteers. In vitro stimulation of alveolar macrophages from healthy control subjects with lipopolysaccharide or pokeweed mitogen led to a time- and dose-dependent enhanced secretion of TNF-alpha, IL-1-beta, and IL-6. In a similar manner, with corresponding cells from patients with sarcoidosis the secretion of all three cytokines could be further increased by stimulation with lipopolysaccharide or pokeweed mitogen. CONCLUSIONS: The data presented indicate that an increased release of TNF-alpha, IL-1-beta, and IL-6 correlates to disease activity and may play a critical part in the pathogenesis of sarcoidosis.     

Sequence-selective biosensor for DNA based on electroactive hybridization indicators

Deoxyribonucleic acid was covalently immobilized onto oxidized glassy carbon electrode surfaces that had been activated using 1-[3-(dimethylamino)-propyl]-3-ethylcarbodimide hydrochloride and N-hydroxysulfosuccinimide. This reaction is selective for immobilization through deoxyguanosine (dG) residues. Immobilized DNA was detected voltammetrically, using tris (2,2'-bipyridyl)cobalt(III) perchlorate and tris (1,10-phenanthroline)cobalt(III) perchlorate (Co(bpy)3(3+) and Co(phen)3(3+). These complexes are reversibly electroactive (1e-) and preconcentrate at the electrode surface through association with double-stranded DNA. Voltammetric peak currents obtained with a poly(dG)poly(dC)-modified electrode depend on [Co(bpy)3(3+)] and [Co(phen)3(3+)] in a nonlinear fashion and indicate saturation binding with immobilized DNA. Voltammetric peak currents for Co(phen)3(3+) reduction were used to estimate the (constant) local DNA concentration at the modified electrode surface; a binding site size of 5 base pairs and an association constant of 1.74 x 10(3) M(-1) yield 8.6 +/- 0.2 mM base pairs. Cyclic voltammetric peak separations indicate that heterogeneous electron transfer is slower at DNA-modified electrodes than at unmodified glassy carbon electrodes. A prototype sequence-selective DNA sensor was constructed by immobilizing a 20-mer oligo (deoxythymidylic acid) (oligo(dT)20), following its enzymatic elongation with dG residues, which yielded the species oligo(dT)20(dG)98. Cyclic voltammograms of 0.12 mM Co(bpy)3(3+) obtained before and after hybridization with poly-(dA) and oligo(dA)20 show increased cathodic peaks after hybridization. The single-stranded form is regenerated on the electrode surface by rinsing with hot deionized water. These results demonstrate the use of electroactive hybridization indicators in a reusable sequence-selective biosensor for DNA.     

The content of asbestos bodies in the bronchoalveolar fluid as a parameter of an increased pulmonary asbestos load

Pulmonary asbestos burdens are usually determined by quantitative pulmonary dust analysis. The aim of this study was to investigate the value of bronchoalveolar lavage (BAL) for this purpose. First, the upper limit of normal for asbestos bodies (AB) in BAL fluid was established using a reference group of 371 patients with no evidence of increased exposure to asbestos. 99% of these patients had less than 0.5 AB/ml. In order to see whether BAL fluid AB concentration reflected pulmonary tissue content, BAL fluid and lung tissue from a further 64 patients with diverse histories of asbestos exposure were investigated. There was a positive association between AB concentration in BAL fluid and lung tissue only for the overall group of 64 patients (r = 0.86; P < 0.001). Twelve of 13 patients with more than 1 AB/ml and ten patients with more than 5 AB/ml had more than 1000 AB/cm3 lung tissue, a value that is usually exceeded in asbestosis. When the upper concentration limit was set at 0.5 AB/ml for BAL fluid and 50 AB/cm3 for lung tissue, only two out of 64 patients had a false positive value (specificity 95%), but eleven patients had false negative results (sensitivity 58%). These investigations establish that concentrations of > or = 0.5 AB/ml are a reliable indicator of increased asbestos exposure and concentrations > 1 AB/ml are associated with a higher probability of having more than 1000 AB/cm3 lung tissue. However, exclusion of increased asbestos exposure is not possible on the basis of negative BAL findings, since the sensitivity of the method is too low.