Beta-adrenergic mechanisms in arterial hemodynamics: A comparison between normotensive and hypertensive rats

The purpose of this study was to determine whether -adrenergically mediated cardiovascular functions such as arterial pressure (AP), heart rate (HR), stroke volume (SV), cardiac output (CO), peripheral resistance (R_p), arterial impedance (Z_c), mean arterial compliance (C_m) and pulse wave reflection (P_b) were altered in the spontaneously hypertensive rat (SHR) compared to the normotensive Wistar Kyoto rat (WKY). In pentobarbital-anesthetized and artificially ventilated rats, the aortic pressure wave was recorded with a high-fidelity Millar sensor, and aortic flow wave with an electromagnetic flow probe. The pressure and flow waves were subjected to Fourier transform so as to analyze impedance spectra. Acute -adrenergic blockade was produced by an intravenous injection of propranolol (nonselective) and atenolol (selective ₁-blocker) at doses of 2 and 5 mg/kg, respectively. Steady-state parameters were obtained 15–20 min after intravenous administration. The SHR had higher AP, HR, R_p and Z_c than the WKY. SV and CO remained unaltered while C_m was lower. In response to propranolol, the mean AP was increased by 7 mm Hg in the WKY, but did not change in the SHR. Moreover, significant decreases occurred in HR, CO and C_m in addition to increases in R_p, Z_c and P_b. These changes between the SHR and WKY were only slight. Atenolol caused decreases in AP, HR and CO in both SHR and WKY, but did not significantly alter the R_p, Z_c, C_m and P_b. Again, the atenolol-induced changes in AP, HR and CO did not appear to be significantly different between SHR and WKY. The results indicate that -adrenergic effects on the heart, Windkessel and resistance vessels are neither greatly enhanced nor impaired during the development of hypertension. In the hypertensive state, significant -adrenergic mechanisms still exert tonic vasodilatory effects on the large and small arterial system.     

AIDS dementia and HIV-1-induced neurotoxicity: Possible pathogenic associations and mechanisms

AIDS Dementia Complex (ADC) is a syndrome of cognitive, behavioral, and motor deficits resulting from HIV-1 infection within the brain. ADC is characterized by variable degrees of neuronal cell death and gliosis that likely result, at least, in part from release of metabolic products, cytokines, and viral proteins from infected macrophages, although a unifying explanation for the neurological dysfunction has yet to be established. Major unanswered questions include: (i) do neurologic symptoms result from neuronal cell death and/or dysfunction in surviving neurons?; (ii) are viral genomic sequences determinants of neurotoxicity?; (iii) is HIV infection of neurons and astrocytes relevant to pathogenesis?, and (iv) what circulating factors within the brain affect neuronal cell survival and function? This review addresses the association between HIV-1 replication within the brain, production of potential neurotoxins and possible mechanisms of induction of neurotoxicity and neuronal dysfunction contributing to the pathogenesis of ADC.     

Differential effects of the stimulation of complement receptors CR1 (CD35) and CR2 (CD21) on cell proliferation and intracellular Ca2+ mobilization of chronic lymphocytic leukemia B cells.

The regulatory role of CR1 and CR2 on B cell activation and proliferation has been investigated by using B cells from patients with chronic lymphocytic leukemia. The chronic lymphocytic leukemia B cells are clonal expansions of B lymphocytes frozen at specific stages of activation. They displayed two patterns of response upon surface Ig (sIg) cross-linking in terms of in vitro proliferation and intracellular free Ca2+ mobilization: cells from patient F (first pattern) proliferated in the presence of mitogenic anti-mu antibodies, whereas cells from patient A (second pattern) did not respond to sIg cross-linking but proliferated in the presence of low m.w. B cell growth factor and IL-2. Coculture of A or F cells with C3b-bearing SRBC led to a two- to four-fold increase in thymidine incorporation in cultures containing low m.w. B cell growth factor but not in cultures containing rIL-2. This enhanced proliferation was inhibited by F(ab')2 polyclonal rabbit antihuman CR1 antibodies. Only cells which proliferated in the presence of anti-mu (cells F) responded to cross-linking of sIg with a rise in intracellular Ca2+. No increase in calcium mobilization was observed after co-cross-linking of CR1 and sIg on A and F cells with mAb or polyclonal anti-CR1 antibodies. Co-cross-linking of CR2 with sIg only led to an enhanced intracellular Ca2+ rise in F cells but not in A cells. The lack of CR2-mediated synergy in Ca2+ rise in A cells indicates that the synergy occurs only if there is a proper coupling of sIg to phospholipase C. CR1-induced proliferation of B cells does not involve the signaling pathways of sIg. These results provide additional evidences for the role of C3 fragments in modulation of human B cell activation.     

Antiidiotypes against autoantibodies in pooled normal human polyspecific Ig

We observed that pooled normal polyspecific human IgG for therapeutic use (IVIg) inhibited the binding of antithyroglobulin, anti-DNA and antiintrinsic factor antibodies to their autoantigens in vitro. The inhibitory effect of IVIg was dependent on interactions between the variable regions of IVIg and variable regions of the autoantibodies. Affinity chromatography of F(ab')2 fragments or of IgG containing anti-TG, anti-DNA, or anti-IF autoantibody activity on Sepharose-bound F(ab')2 from IVIg resulted in the specific retention of autoantibody activity, indicating that IVIg contain antiidiotypic antibodies against human autoantibodies. Inhibition of autoantibody activity by anti-Id in IVIg in vitro is dose dependent with maximal inhibition occurring at a specific molar ratio between patient's IgG and IVIg and shows a prozone phenomenon. The relative content in anti-Id against a particular autoantibody may differ between IVIg preparations. Affinity chromatography of IVIg on Sepharose-bound F(ab')2 fragments from IVIg also resulted in specific retention of anti-TG and anti-DNA activities that were found to be present in pooled normal immunoglobulins. The presence in IVIg of anti-Id against autoantibodies from patients and from normal individuals may provide a mechanism for the suppressive effect of IVIg in human autoimmune diseases and supports the concept of a functional idiotypic network regulating autoimmune responses in man.     

The effect of polymyxin B and some mast-cell constituents on mucosal mast cells in the duodenum of the rat

Summary Mucosal mast cells in the rat duodenum show no morphological signs of exocytosis of granules and do not release histamine after treatment with polymyxin B in doses large enough to cause almost complete degranulation of connective-tissue mast cells of tongue, skin, and mesentery with concomitant release of 60% of the tissue histamine. Administration of polymyxin B in gradually increasing doses over a period of 5ds resulted in a statistically significant increase in mucosal mast cells and a comparable increase in duodenal histamine content, whereas the connective-tissue mast cells in the other tissues examined became fewer in number, the remaining cells showing profound morphological changes, and tissue histamine levels, were reduced to 40% of the controls. A similar increase in mucosal mast cells has been observed after treatment with another mast-cell secretagogue, compound 48/80. This suggests that the increase in mucosal mast cells may be an indirect effect of these compounds, related to their activation of other mast cells and mediated by material(s) secreted by the connective-tissue mast cells. Possible mediators such as heparin, histamine, and 5-hydroxytryptamine injected for 5 ds in doses large enough to account for the amount released from the degranulated mast cells had no effect on the morphology or numbers of mast cells in any of the tissues examined.Supported by grants from the Swedish Medical Research Council, Project no 2235     

Expression, molecular association, and functions of C3 complement receptors CR1 (CD35) and CR2 (CD21) on the human T cell line HPB-ALL.

We have investigated the expression, molecular association, ligand binding properties, and ability to transduce intracellular signals of CR1 and CR2 C3 receptors on cells of the human HPB-ALL T cell line. CR1 and CR2 on HPB-ALL cells bound polymeric C3b and C3dg and several anti-CR1 and anti-CR2 mAb recognizing different epitopes of the receptors on normal peripheral blood cells. Immunoprecipitated CR1 and CR2 exhibited similar m.w. to those of the receptors on normal peripheral blood T and B lymphocytes. CR1 and CR2 were partially associated in the form of CR1/CR2 complexes in the cell membrane as assessed by the ability of the receptors to cocap and cointernalize and to form a detergent-sensitive complex upon immunoprecipitation analysis. Triggering of CR2 with mAb OKB7 that recognizes an epitope associated with the ligand binding site of the receptor induced an increase in intracellular free calcium concentration in HPB-ALL cells. The signal provided by mAb OKB7 did not synergize with that triggered by anti-CD3 mAb UCHT1. Triggering of CR1 did not result in changes in intracellular free calcium concentration. Our observations have significance for the biology of normal human T cells because the majority of peripheral blood T cells that express CR1 also expressed CR2 and because a change in (Ca2+)i was induced by mAb OKB7 in purified normal T cells. These functions may be relevant for the regulatory role of C3 fragments on the immune response to T-dependent Ag and for the penetration into T cells of lymphocytotropic viruses.     

Psychiatric case finding in Ethiopia: Shortcomings of the self reporting questionnaire

Attenders of health care facilities usually present somatic complaints. It is important to identify the psychiatric patients among them, especially the neurotic complainers. They are at risk for being exposed to expensive somatic investigations and being prescribed useless and sometimes harmful drug treatment. The World Health Organization designed the Self Reporting Questionnaire (SRQ), to be a universally applicable psychiatric case finding instrument, for use in medical clinics. A feasibility study with this instrument was carried out with 110 respondents in Ethiopia. A moderate criterion validity was found, limitations being partly due to the sensitivity of the SRQ to help-seeking behavior, even in the absence of any mental illness. This study also revealed problems in transcultural communication because many of the diagnostic concepts used in this instrument were too western to be transposed unchanged to the Ethiopian culture. Items need fairly extensive modification to be applicable there.     

Alternating immunochemotherapy of advanced gastric carcinoma: A randomized comparison of carbazilquinone and PSK to carbazilquinone in patients with curative gastric resection

A total of 103 patients with advanced gastric carcinoma were randomized after curative surgery to receive an alternate administration of carbazilquinone (CQ and PSK (Krestin) or carbazilquinone alone. Each course of therapies started 1 week after the surgical operation and therapy schedules consisted of 9 courses. In each course of 6 weeks, CQ (2 mg/m²/week) was administered on day 0, 8, and 15. In combined immunochemotherapy group, PSK was given orally in 3-divided doses of 2 g/m²/day from the day of the third CQ administration for consecutive 4 weeks. Estimated survival rate and cumulative survival curve were compared utilizing the data up to 7 years after the operation. There was no overall significant difference in survival rates between the CQ plus PSK group and the CQ alone group, but a group of patients whose disease was classified as S₁ + S₂(N_1–2) survived significantly longer when treated with the combination of CQ and PSK. Neither in more advanced cases (> S₃ or > N₃) nor in cancers of early stages, the addition of PSK provided an additive effect. The favorable result obtained in one subgroup treated with PSK, suggests that the use of this agent in treating gastric cancers should be carefully evaluated in terms of serosal infiltration and nodal metastasis.