Congestive cardiac failure in a 65-year-old man.
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Aged↗
Biomedical subjects
R Mathew
Publications and source records attributed to R Mathew.
Characterization of mycobacterial antigens and antibodies in circulating immune complexes from pulmonary tuberculosis.
Circulating immune complexes (CICs) in serum samples from patients with pulmonary tuberculosis (bacteriologically positive [S+C+] and bacteriologically negative [S-C-]) and controls (NHC) have been measured by using C1q binding assay (C1qBA) and 3.5% polyethylene glycol precipitation and measurement of absorbance at 280 nm (PEG-OD 280). Although C1qBA did not show any difference between tuberculous and normal serum samples, PEG-OD 280 was significantly elevated in tuberculous samples. The effect of chemotherapy on CIC levels was studied. During the treatment, initially (for up to 2 months) there was a rise in CIC levels and later a fall, coinciding with bacterial clearance. Anti-purified protein derivative antibodies of class immunoglobulin G (IgG) and immunoglobulin M were measured in the serum samples and PEG precipitates. Anti-mycobacterial antibody measurement in CICs was more discriminatory between the groups than serum antibody. For characterization of the complexed antibody, the PEG precipitates were used in the Western blot and the patterns were compared. S+C+ CICs contained antibodies for a wide range of antigens ranging from 100 Kd to 10 Kd. However, none of the NHC-CICs contained antibodies for antigens < 70 Kd. Thus, when using the criterion of positivity for antibodies to antigens < 70 Kd as a marker for pulmonary tuberculosis, 24 of 24 (100%) of the S+C+ CICs were positive. Similarly, 11 of 16 (70%) of the S-C- CICs contained antibodies for antigens < 70 Kd.(ABSTRACT TRUNCATED AT 250 WORDS)
Antibodies, Bacterial↗
Role of nitric oxide and endothelin-1 in monocrotaline-induced pulmonary hypertension in rats.
OBJECTIVE: Nitric oxide (NO) and endothelin-1 (ET-1) have both been implicated in the pathogenesis of pulmonary hypertension (PH). Therefore, we examined NO-related relaxation and ET-1 levels in rat hilar pulmonary arteries (PA) during the progression of monocrotaline (MCT)-induced PH. METHODS: Rats were studied 1 and 2 weeks after a single subcutaneous injection of MCT (80 mg/kg). Pulmonary artery pressure (PAP), right ventricular hypertrophy (RVH), NO-related relaxation and tissue ET-1 levels in PA were evaluated and compared with control (C). RESULTS: One week post-MCT, endothelium (E)-dependent relaxation to 10(-5) M adenosine diphosphate (ADP), 10(-5) M A23187 and 10(-5) M acetylcholine (ACh) and tissue ET-1 levels in PA were normal. Rats in this group did not develop PH or RVH. Two weeks post-MCT, E-dependent relaxation was impaired (ADP, 7 +/- 3% VS. c, 62 +/- 5%; A23187, 2 +/- 7% vs. C, 58 +/- 2%; ACh, 33 +/- 7% vs. C, 86 +/- 2%; P < 0.05) and ET-1 levels were elevated (1925 +/- 244 pg/g wwt vs. C, 469 +/- 59 pg/g wwt, P < 0.05), In addition, significant PH and RVH were present (PAP 33 +/- 4 mmHg vs. C 18 +/- 0.8 mmHg, P < 0.05; RVH index 0.40 +/- 0.006 vs. C, 0.25 +/- 0.01, P < 0.05). Incubation with 10 microM indomethacin, 150 U/ml superoxide dismutase or 300 microM L-arginine failed to restore impaired relaxation to ACh. In E-intact rings, relaxation to 10(-6) M glyceryl trinitrate (GTN) was inhibited at 1 week post-MCT (72 +/- 2% vs. C, 87 +/- 3%, P < 0.05) with further inhibition at 2 weeks (39 +/- 4%). Response to GTN in E-denuded rings was normal in MCT groups. CONCLUSIONS: These results indicate that MCT injection in rats results in delayed but progressive endothelial injury and PH. Despite mild endothelial dysfunction 1 week post-MCT, NO-related relaxation and ET-1 levels are normal. At 2 weeks post-MCT, inhibition of E-dependent NO-related relaxation and elevation of ET-1 levels are associated with PH and RVH. Thus inhibition of NO production associated with elevated ET-1 levels may play an important role in the pathophysiology of MCT-induced PH.
Acetylcholine↗
Furazolidone in typhoid fever--correlation of clinical efficacy with serum bactericidal activity.
Treatment of typhoid fever with furazolidone produces a high cure rate. This is a clinical curiosity, as furazolidone is described to be poorly absorbed. The present study examined whether furazolidone could produce unequivocal clinical response and, if so whether this was due to the drug producing bactericidal levels in the serum. Twenty one patients selected by defined criteria were treated with furazolidone and evaluated for definite clinical response in 5-7 days. Bactericidal activity of pre dose and post dose sera were estimated in seven patients showing definite clinical response. All the seven patients had a clinical cure without the drug producing significant bactericidal levels in the blood. Hence we concluded that the major site of action of furazolidone was in the intestine. It is our postulate that the organisms reaching the intestine in large numbers from bile are prevented from gaining re-entry into the circulation by the action of furazolidone in the intestine. After repeated cycles of entry of organisms into the intestine from bile and the simultaneous prevention of its re-entry into the circulation, the number of organisms remaining in circulation comes down considerably, thus helping the immune system to bring about a cure.
Anti-Infective Agents↗
Nursing care of infants on phototherapy.
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Humans↗
Magnesium and heart.
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Arrhythmias, Cardiac↗
The other side of coronary artery disease.
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Coronary Disease↗
IL-2 contributes to the IL-5 response in granulomas from mice infected with Schistosoma mansoni.
Th cells within the granulomas of murine schistosomiasis mansoni produce IL-5, which is essential for granuloma eosinophil growth and development. The mechanisms regulating granuloma IL-5 production are unknown. The granulomas also make IL-2 in small quantities. rIL-2 therapy stimulates eosinophilia and IL-5 synthesis. Therefore, we studied the effect of IL-2 on IL-5 production within the liver granulomas of murine Schistosoma mansoni. Dispersed granuloma cells and intact granulomas cultured in vitro released IL-5. Adding anti-IL-2 or anti-IL-2R to the cultures, to block IL-2 activity, significantly inhibited IL-5 production. However, supplementing the cultures with small quantities of rIL-2 markedly stimulated IL-5 release in a dose-dependent fashion. Blocking anti-IL-4 mAb had no effect. Also, granuloma T cells were isolated by FACS. These highly purified T cells produced IL-5 both in the presence and absence of plate-bound anti-CD3. Once again, the IL-5 production was dependent on IL-2. The requirement of IL-2 for normal IL-5 production was not dependent on an IL-2-induced expansion of the IL-5-producing, T lymphocyte population. Thus, IL-2 mediates T cell interactions within the granuloma that regulate granuloma IL-5 secretion.
Animals↗
Modulation of T lymphocyte proliferation in mice infected with Schistosoma mansoni: VIP suppresses mitogen- and antigen-induced T cell proliferation possibly by inhibiting IL-2 production.
Mice infected with Schistosoma mansoni mount focal granulomatous responses around each ovum that deposits in the liver and intestinal wall. The granulomas ultimately destroy the ova while absorbing the released toxic, injurious agents. The granulomas contain T cells and other cell types, all of which are under control. For example, T lymphocyte proliferation in situ within the granulomas is probably restrained by various regulatory mechanisms. Granuloma eosinophils make VIP, and granuloma T cells have VIP receptors. Yet, the function of VIP within the granulomatous response is unknown. We studied the effect of VIP on granuloma and splenic T cell proliferation in response to Con A or soluble egg antigens (SEA). [3H]Thymidine incorporation was used to assess the rate of proliferation. VIP decreased Con A- or SEA-induced, T lymphocyte proliferation. Suppression of proliferation was most evident for T cells stimulated submaximally with mitogen or antigen. Since T lymphocyte proliferation in response to antigen or mitogen requires soluble lymphokines, we investigated the capacity of VIP to alter the expression of several lymphokines as a possible mechanism for mediating suppression of T cell proliferation. VIP decreased IL-2 production, but did not effect IL-5 or IFN-gamma release. The effect of VIP on IL-2 production was dependent on the presence of a CD4+ T lymphocyte subset. VIP could no longer modulate lymphocyte proliferation if exogenous rIL-2 was added to the cultures. The addition of neutralizing anti-IL-2 mAb, but not anti-IL-4 mAb, substantially decreased granuloma lymphocyte proliferation in response to antigen or mitogen. This suggested that granuloma T cell proliferation required endogenously produced IL-2. These findings suggest that VIP may help modulate granuloma T cell proliferation through regulation of IL-2 production.
Animals↗
Lymphokine expression in granulomas of Schistosoma mansoni-infected mice.
Lymphokine mRNA for IL-2, IL-4, IL-5, IL-10, and IFN-gamma was identified in total RNA, extracted from granuloma and spleen cells of Schistosoma mansoni-infected mice. The specific mRNA in these preparations was identified after reverse transcription and polymerase chain reaction amplification. In some experiments, spleen cells were incubated in the presence of soluble egg antigens or mitogen before RNA extraction. Also, the secretion of these lymphokines from cells maintained in vitro was measured by ELISA or bioassay. The spleen cells from either uninfected or infected mice constitutively released no detectable cytokines and expressed only IL-10 mRNA prominently. Mitogen induced spleen cells from either source to express IL-2 and IFN-gamma mRNAs and their corresponding proteins. Also, spleen cells from noninfected mice stimulated with mitogen expressed IL-4 mRNA, but not IL-5 mRNA, and no detectable protein products. Yet, IL-5 was inducible in spleen cells from infected animals. Soluble egg antigens induced spleen cells from infected mice to prominently express a variety of cytokine genes and produced large amounts of cytokine proteins, but spleen cells from uninfected mice did not respond. Unlike the spleen, the granulomas constitutively expressed mRNAs for all the cytokines examined. Yet, there was limited expression of IL-2 mRNA as compared to that of other cytokines. Except for IL-5, unfractionated granuloma cells constitutively released cytokines at low or undetectable levels. Soluble egg antigens or mitogen enhanced the production of all cytokines to different extents. These observations indicate that schistosome granulomas and spleens express both Th1 and Th2 cytokines. The various lymphokines display complex differences in both lymphokine mRNA and product expression. These results suggest that the production of granuloma lymphokines is governed selectively, possibly by a variety of undetermined regulatory pathways.
Animals↗
Congestive heart failure alters receptor-dependent cAMP-mediated relaxation of canine pulmonary arteries.
BACKGROUND: Alterations in myocardial function and systemic vascular tone are well documented in congestive heart failure (CHF), but little information is available on the effects of CHF on pulmonary vessels. We examined the mechanisms of tone regulation of canine pulmonary arteries during pacing-induced CHF. METHODS AND RESULTS: Rings 3-4 mm wide from lobar pulmonary arteries were prepared from normal dogs, dogs paced at 210 beats per minute for 3 weeks (paced group, nonfailure), and dogs also paced at 240 beats per minute during the fourth week to induce severe heart failure (CHF group). Contractile responses to 60 mmol/L KCl and phenylephrine and relaxation responses to acetylcholine, bradykinin (endothelium-dependent cyclic GMP [cGMP]-mediated), isoproterenol, arachidonic acid, prostacyclin (receptor-dependent cyclic AMP [cAMP]-mediated), forskolin (direct stimulator of adenylate cyclase), a forskolin analogue (devoid of adenylate cyclase-dependent activity), and RO 20-1724 (phosphodiesterase inhibitor) were characterized. The paced group did not show alterations in vascular reactivity. Contractile response to phenylephrine and cGMP-mediated relaxation responses were not altered in the CHF group; however, receptor-mediated cAMP-induced relaxation responses were significantly inhibited (p < 0.05). Relaxation responses to isoproterenol (10(-6) mol/L), arachidonic acid (10(-5) mol/L), and prostacyclin (10(-5) mol/L) were reduced by 56%, 72%, and 74%, respectively. The relaxation response to RO 20-1724 was not affected by CHF, and this probe did not enhance the impaired relaxation response to isoproterenol. Forskolin-induced relaxation was not altered, and the forskolin analogue produced minimal relaxation compared with forskolin. CONCLUSIONS: These findings suggest that in pacing-induced CHF, canine pulmonary arteries show a selective defect in receptor coupling to cAMP-dependent relaxation mechanisms. There is no evidence of enhanced degradation of cAMP.
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
Murine mucosal T cells have VIP receptors functionally distinct from those on intestinal epithelial cells.
Reports suggest that vasoactive intestinal peptide (VIP) binds to lymphocytes and modulates immune responses. The intestines are richly innervated with VIP-producing nerves. Thus, VIP from nerves or other sources may participate in mucosal immunoregulation. To explore this hypothesis further, murine intestinal mucosal inflammatory cells were scrutinized for functional VIP receptors. An [125I]VIP competitive binding assay characterized VIP receptors. Unfractionated lamina propria inflammatory cells bound [125I]VIP specifically. This binding was abrogated by T cell depletion. The VIP receptor on lamina propria T cells was of a single class with a Kd of 9.08 x 10(-9) M. It bound PHI and other peptide analogs poorly. The intestinal epithelial cell had a high-affinity VIP receptor (Kd 4.17 x 10(-10) M) that bound one VIP analog with moderate affinity. Both VIP and ConA stimulated mucosal inflammatory cells to release interleukin-5 (IL-5). Mucosal inflammatory cells depleted of T cells did not release IL-5 in response to VIP or ConA. It is concluded that: (1) some murine mucosal T lymphocytes have VIP receptors that may be distinct from those displayed on mucosal epithelial cells; (2) VIP affects mucosal T lymphocyte function.
Animals↗
Activity staining of endoglucanases in polyacrylamide gels.
The endoglucanases of Penicillium funiculosum were analyzed for the presence of multiple forms using a modified version of the Congo red method. Postelectrophoretic slab gels were directly incubated in a solution of carboxymethylcellulose for a period as short as 15 min and then the activities were visualized by staining with Congo red. Ten distinct bands of clearances were obtained indicating the presence of at least as many multiple forms.
Acrylic Resins↗
TCR induced expression of Fc receptors on murine T cell subsets in vitro and in vivo.
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Animals↗
Role of cGMP mechanisms in response of rat pulmonary arteries to hypoxia.
We have demonstrated previously that in response to hypoxia, isolated rat pulmonary arteries show an initial endothelium-dependent relaxation followed by an endothelium-independent transient contraction. In the presence of increased extracellular Ca2+, both of these responses were enhanced in endothelium-intact arteries. Nitro-L-arginine, a blocker of the biosynthesis of endothelium-derived relaxing factor (EDRF), abolished the initial endothelium-dependent relaxation and Ca(2+)-induced enhancement of hypoxic contraction in endothelium-intact arteries but did not alter responses in endothelium-denuded vessels. Inhibition of prostaglandin formation with indomethacin had no effect on the hypoxia-elicited responses. Preincubation with LY 83583, an inhibitor of guanylate cyclase activation, abolished the initial hypoxia-elicited relaxation and subsequent contraction. M & B 22948, a guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor, decreased tone under O2 but not under N2, causing an apparent enhancement of the contraction to hypoxia. Thus the modulation of hypoxic responses by the endothelium is dependent on changes in EDRF production, and a decrease in smooth muscle cGMP not involving an EDRF mechanism appears to mediate the endothelium-independent hypoxic contraction observed in the isolated rat pulmonary artery.
Aminoquinolines↗
Quantitation of microsomal alpha-hydroxylation of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is activated to DNA alkylating species via two different alpha-hydroxylation pathways. Methylene hydroxylation leads to DNA methylation, whereas methyl hydroxylation yields DNA pyridyloxobutylation. We have developed a high-pressure liquid chromatography assay utilizing radiochemical detection that permits the determination of the extent of metabolism through each pathway in microsomal preparations. Levels of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) were used to measure the extent of methyl hydroxylation, whereas levels of the aldehyde, 4-oxo-1-(3-pyridyl)-1-butanone (OPB), were used to quantify the extent of methylene hydroxylation. Incubations of [5-3H]NNK with microsomes and cofactors were conducted in the presence of 5 mM sodium bisulfite to trap the reactive OPB. The inclusion of bisulfite did not affect the rate of NNK metabolism. Trapping the aldehyde also inhibited its further oxidation to the corresponding acid or reduction to HPB. Furthermore, the conversion of HPB to OPB made only a minor contribution to the OPB levels under our incubation conditions. Analysis of incubation mixtures containing [5-3H]NNK, cofactors, and either A/J mouse liver or lung microsomes demonstrated that OPB was a significant metabolite of NNK. The OPB:HPB ratio was greater in liver (1.5) than in lung (0.2-1) microsomal preparations. Apparent Km values for OPB and HPB formation in lung microsomes were 23.7 and 3.6 microM, respectively, whereas the corresponding values for liver microsomes were 19.1 and 73.8 microM, respectively. These data are consistent with the involvement of more than one cytochrome P-450 isozyme in the activation of NNK to DNA reactive species.
Animals↗
In vivo and in vitro persistence of pyridyloxobutyl DNA adducts from 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.
The persistence of pyridyloxobutyl DNA adducts in lung and liver of F-344 rats treated with the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was investigated. The levels of these adducts were determined at various time points up to 4 weeks post s.c. injection of [5-3H]NNK (0.8 mg/kg body wt). Maximal levels of the adducts were observed between 4 and 24 h in both tissues. The disappearance of the adducts from lung and liver DNA was multiphasic with initial half-lives of 50 and 38 h respectively. In both cases, detectable levels of the pyridyloxobutyl adducts were observed at 4 weeks post injection. The in vitro rate of adduct disappearance was studied using calf thymus DNA reacted with 4-(acetoxymethylnitrosamino)-1-(3-[5-3H]pyridyl)-1-butanone in the presence of esterase. Adduct levels were measured for up to 2 weeks after the initiation of the experiment. The decomposition of these adducts was triphasic with half-lives of 6, 120 and 430 h. The multiphasic disappearance of the pyridyloxobutyl adducts suggests that there is more than a single adduct generated upon pyridyloxobutylation of DNA and that at least one of these adducts has a significant lifetime in DNA.
Animals↗
O2 and rat pulmonary artery tone: effects of endothelium, Ca2+, cyanide, and monocrotaline.
The present study examines the influence of the endothelium (E), Ca2+ concentration, cyanide and monocrotaline (MCT) pretreatment on the responses of isolated rat hilar pulmonary arterial rings (PA) to hypoxia. In PA precontracted with phenylephrine, hypoxia induced an initial E-dependent relaxation phase followed by an E-independent transient contraction and a final relaxation. An increase in Ca2+ concentration from 1.5 to 2.5 mM produced an E-dependent reduction in tone generation under O2 and a significant enhancement of the hypoxia-elicited initial relaxation and the transient contractile responses. Addition of cyanide (0.1 mM) to precontracted PA produced a transient contraction similar to that caused by hypoxia. Preincubation with cyanide led to inhibition of tone generation and abolition of the contraction to hypoxia. However, the final relaxation response to hypoxia was not inhibited by cyanide. Thus, hypoxia produces an E-independent contraction via a mechanism that appears also to be activated by cyanide, and this response is not altered by MCT. The endothelium alters the response to hypoxia in a Ca(2+)-dependent manner.
Acetylcholine↗