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PubMed1978

Milk precipitins, circulating immune complexes, and IgA deficiency.

Twenty-two patients with selective IgA deficiency were studied for the presence of serum precipitins to bovine milk, bovine and fetal calf serum, and circulating immune complexes. Fifty-nine percent had circulating immune complexes, 50% had milk precipitins, 23% had precipitins to bovine serum, and 13% had precipitins to fetal calf serum. All patients with precipitating antibodies against milk or against bovine or fetal calf serum had circulating immune complexes and the precipitin titers correlated with the amount of circulating immune complexes. After one IgA-deficient patient had drunk 100 ml of milk, studies of sequential serum samples showed the presence of casein in the circulation at 60 min and the appearance of increasing amounts of immune complexes for 120 min. These findings are interpreted to indicated that in human beings the IgA system may provide a major barrier to absorption of immunogens from the gastrointestinal tract.

Adult↗

PubMed2005

Patients with atherosclerosis may have increased circulating levels of 27-hydroxycholesterol and cholestenoic acid.

Extrahepatic sterol 27-hydroxylase (CYP27) appears to have a role in the elimination of excess cholesterol from various cells, particularly macrophages, and there is a net flux of 27-hydroxyycholesterol and its metabolites from different extrahepatic sources to the liver. In this study we tested the hypothesis that patients with advanced atherosclerosis may have higher levels of 27-oxygenated products in the circulation than control subjects. Concordant with previous studies, a strong correlation was observed between circulating levels of 27-hydroxycholesterol and cholesterol, in both healthy subjects and subjects with hypercholesterolemia and documented atherosclerosis. A group of male subjects with normal or only slightly elevated serum cholesterol and rapidly progressing carotid atherosclerosis (n = 20) had serum levels of 27-oxygenated cholesterol not statistically different from those of a matched group of subjects with little or no development of atherosclerosis (n = 20). The situation was similar in a group of patients (n = 20) with advanced general atherosclerosis associated with severe clinical symptoms. Among the two groups of patients with atherosclerosis, a few patients had relatively high levels of 27-oxygenated products. Among the healthy controls, two healthy volunteers (brother and sister) were found to have high levels of 27-hydroxycholesterol, most probably due to genetic reasons. The possibility is discussed that the high levels of 27-oxygenated products in the circulation of a few patients with atherosclerosis may be related to high amounts of active macrophages present in atherosclerotic lesions. In view of the number of factors that could affect the levels in the circulation, other explanations cannot be ruled out. At the present state of knowledge, measurements of circulating levels of 27-oxygenated metabolites do not seem to add useful information about the atherosclerotic process.

Arteriosclerosis↗

PubMed2006

Circulating apoptotic proteins are increased in long-term disease-free breast cancer survivors.

Circulating apoptotic proteins are increased in patients with heart failure. We evaluated whether circulating soluble (s) apoptosis-related proteins and inflammation markers are increased in long-term disease free breast cancer survivors and associated with cardiotoxicity, and if subgroups could be identified based on the applied treatments. Circulating tumour necrosis factor (TNF) alpha, sTNF-receptor (sTNF-R) 1 and 2, sFas, sFas ligand, sTNF-related apoptosis inducing ligand (sTRAIL) and serum HER2 were measured with immunoassay. High-sensitivity C-reactive protein (HS-CRP), fibrinogen, plasma B-type and N-terminal atrial natriuretic peptide (NT-ANP and BNP) were also determined. Thirty-four patients with median 6.0 years follow-up and 12 healthy age-matched women were enrolled. Chemotherapy, consisting of five cycles fluorouracil, epirubicin (90 mg/m(2)), cyclophosphamide (FEC) (n=14) or four cycles FEC followed by myeloablation with high-dose carboplatin, cyclophosphamide, thiotepa (n=20), preceded irradiation and tamoxifen. Circulating apoptosis markers were higher in patients than in controls. No associations with cardiac dysfunction were observed. sFas ligand and sTRAIL were higher in the high-dose than in the standard-dose group. In conclusion, we observed increased circulating apoptotic protein levels in long-term disease-free breast cancer survivors, treated with adjuvant chemoradiotherapy, particularly after myeloablative chemotherapy. The potential relation with late cardiotoxicity of antineoplastic therapy deserves further study.

Adult↗

PubMed2002

Quantitative real-time polymerase chain reaction for detection of circulating cells with t(14;18) in volunteer blood donors and patients with follicular lymphoma.

The chromosomal rearrangement t(14;18)(q32;21) involves the major (MBR) or minor (mcr) breakpoint cluster regions and the immunoglobulin heavy chain joining regions (JH) in most follicular lymphomas. As a first step towards determining the clinical significance of circulating cells with t(14;18), we detected and quantitated circulating cells in samples obtained from volunteer blood donors and follicular lymphoma patients. The t(14;18) was co-amplified with beta-actin with real-time quantitative PCR (QRT-PCR) in reactions containing 1 microg of DNA from peripheral blood or bone marrow aspirates. The cell number was quantitated using linear regression and an external standard of serially diluted DNA from cell lines with MBR/JH or mcr/JH rearrangements. At dilutions of 10(5) and 106, sensitivity was 100 and 55% for MBR/JH, and 100 and 10% for mcr/JH rearrangements. Among 102 volunteer blood donors MBR/JH vs. mcr/JH amplicons were detected in 22 vs. 4% with duplicate 1 microg DNA reactions, and in 41 vs. 6% with a total 10 microg DNA analyzed in multiple reactions. Among volunteer blood donors the mean number of circulating cells with MBR/JH vs. mcr/JH rearrangements were 0.8 vs. 0.1/microg DNA, and exceeded the upper normal limit (defined as the mean of all volunteer samples plus two standard deviations) in 3% vs. 2%, respectively. Analysis for MBR/JH rearrangements revealed that follicular lymphoma patients vs. volunteer blood donors were positive in 76% vs. 22% (p = 0.008 by Fisher's exact test); that the mean number of MBR/JH cells per microg of DNA was 91 vs. 0.8 (p = 0.0002 by Mann-Whitney test); and the number of the MBR/JH cells exceeded the upper normal limit in 32% vs. 3% of subjects (p = 0.0001 by Fisher's exact test). Circulating cells with mcr/JH were not detected among any of these 25 lymphoma patients. We conclude that patients with follicular lymphoma are more frequently positive, have higher numbers of circulating cells with t(14;18), which exceed upper normal limit more frequently than in volunteer blood donors.

Blood Cells↗

PubMed1977

Features of systemic lupus erythematosus in mice injected with bacterial lipopolysaccharides: identificantion of circulating DNA and renal localization of DNA-anti-DNA complexes.

After injection of lipopolysaccharides (LPS) in mice, there is first a release of DNA into plasma and secondly an induction of anti-DNA antibodies. The circulating DNA was purified from plasma and physico-immunochemically characterized. This DNA has a similar density to mammalian cellular DNA,is 4--6S insize, and probably represents a mixture of single-stranded DNA (SSDNA) and double-stranded DNA (DSDNA) or DSDNA with some single-stranded regions. This purified DNA was shown to react with anti-DNA antibodies which appeared as early as 3 days after a single injection of LPS in mice. In serum, DNA-anti-DNA complexes were not detected, although unidentified circulating immune complex-like material was demonstrated 5-8 days after the injection of LPS. In tissues, particularly in renal glomeruli, fine granular immune complex-type immunoglobulin deposits appeared along the glomerular capillary walls and in the mesangium 3 days after the injection of LPS. There is a direct correlation between the level of anti-DNA antibodies and the intensity of glomerular deposits and about 40% of immunoglobulins eluted from kidneys are anti-DNA antibodies, indicating that some of the immune complexes localized in kidneys are DNA-anti-DNA complexes. Based on these observations, the following hypothetical mechanism for the glomerular localization of DNA-anti-DNA complexes after the injection of LPS in mice is proposed. First, DNA, which has been released in circulating blood after injection of LPS, might bind to renal glomeruli, probably on glomerular basement membranes (GBM) through a high affinity of GBM for DNA; secondly, circulating anti-DNA antibodies, which appear later, might react with the glomerular-bound DNA and form immune complexes independently of circulating immune complexes. However, the possibility of direct deposition of immune complexes is not ruled out.

Animals↗

PubMed1996

Circulating progenitor cells in human ontogenesis: response to growth factors and replating potential.

We have measured the number of progenitor cells circulating in fetal (17-32 weeks of gestation), perinatal (36 weeks of gestation), and adult (30-50 years old) blood. The progenitor cells at each ontogenetic stage were also characterized in terms both of the minimal combinations of growth factors they required to form maximal numbers of colonies in vitro and of their self-replication potential, as measured by the number of secondary and tertiary progenitor cells each could generate. The number of progenitor cells circulating in fetal and perinatal blood can be measured by directly plating the unfractionated blood. In this assay, fetal blood contains half the number of progenitor cells detected in perinatal blood (18.0 +/- 16.4 versus 40.88 +/- 0.63, p < 0.01), and the number of progenitor cells in adult blood is below the level of detection of the assay (< 1/8 microliter of blood). To compare the number of progenitor cells in all three stages of human development, progenitor cell counts were performed on blood mononuclear cells enriched by density separation. In this case, the light density cell fractions from fetal and neonatal blood contained the same number of progenitor cells (300/10(5) cells), numbers that were 10-fold higher than those observed with adult blood (30/10(5) cells). Circulating fetal-neonatal erythroid and multipotential progenitor cells were found to differ from their adult counterparts in terms of their response to growth factors and their self-renewal ability. In fact, the number of cytokines required to observe maximal colony formation increased with the ontogenetic stage of the cells. No differences were found in the frequency of primary colonies containing progenitor cells or in the mean number of secondary progenitor cells per primary colony in cultures of fetal, neonatal, or adult blood. Differences between the three ontogenetic stages, however, were found with respect to the number of sequential replatings that were possible. In fact, although both secondary granulocyte-macrophage (GM) and mixed-cell colonies derived from fetal cells gave rise to tertiary colonies, only perinatal secondary mixed-cell colonies grew in tertiary cultures, and no growth was observed in tertiary cultures of adult cells. These results suggest that the greater amplification of progenitor cells observed in liquid culture of fetal/neonatal versus adult blood is due both to a higher proliferative capacity of neonatal progenitor cells (up to two replatings versus one) and to a higher frequency in these samples of mixed-cell colony-forming cells (CFC) (37.7 +/- 7.3 versus 2.0 +/- 0.7/10(5) light density cells, respectively). Because of the high numbers of progenitor cells circulating in the fetus, as well as their high proliferative capacity, it is predicted that if blood could be harvested directly in utero, fetal blood would be as good a source of stem cells for transplantation as perinatal placental/cord blood. Circulating fetal stem cells would, therefore, represent an ideal target for gene therapy and in utero autologous transplantation.

Adult↗

PubMed2001

Potential clinical value of circulating chromogranin A in patients with prostate carcinoma.

BACKGROUND: Neuroendocrine (NE) differentiation of prostate adenocarcinoma has received increasing attention in recent years as a result of possible implications for prognosis and therapy. The presence of NE tumor subpopulation can be gauged non invasively by measuring circulating levels of secretory products, primarily chromogranin A (CgA). METHODS: This article provides a review on published papers evaluating circulating CgA in prostate cancer patients. RESULTS: Circulating CgA levels were found to be higher in prostate cancer patients than in patients with benign or pre-malignant prostatic diseases. In patients with malignancy, they correlated either to the stage of disease or to the condition of hormone refractoriness. CgA levels did not correlate with serum prostate specific antigen (PSA) and were supranormal in the majority of advanced patients with PSA within normality. In hormone refractory cases, elevated CgA was a significant predictor of poor prognosis, independently from serum PSA. CgA values were not substantially affected by either endocrine therapy or chemotherapy. They were found to increase during androgen deprivation in some cases and this trend preceded that of PSA. The administration of a somatostatin analog in hormone refractory cases was able to reduce plasma CgA values consistently. CONCLUSIONS: Present data suggest a potential role of circulating CgA in the management of prostate cancer patients. CgA determination may be useful diagnostically and prognostically and could offer complementary information with respect to PSA. Serial evaluation of circulating CgA could provide information on changes in the NE phenotype expression as a consequence of tumor progression and/or treatment administration.

Androgen Antagonists↗

PubMed2005

Total and differential white blood cell counts and their associations with circulating interleukin-6 levels in community-dwelling older women.

BACKGROUND: Interleukin-6 (IL-6) is an inflammatory biomediator, and age-related increases in IL-6 levels are associated with osteoporosis, sarcopenia, disability, and mortality in older adults. Although white blood cells (WBC), or leukocytes, are known to produce IL-6 in vitro, their in vivo relationship with circulating IL-6 levels is not well established. METHODS: In this cross-sectional analysis of data from the Women's Health and Aging Study I, the authors evaluated the relationships of total WBC and WBC differential (neutrophil, monocyte, lymphocyte, eosinophil, and basophil) counts to circulating IL-6 levels in 619 community-dwelling older women. Potential associations of age, race, and cigarette smoking with total and differential WBC counts and IL-6 levels were also assessed. RESULTS: Except for lymphocyte and basophil counts, significant associations of total WBC, neutrophil, monocyte, and eosinophil counts with IL-6 levels were identified. These associations remained highly significant after adjustment for age, race, and smoking status. Total WBC, neutrophil, monocyte, and eosinophil counts had significant stepwise increases in four escalating quartiles of IL-6 levels. In addition, age, race, and cigarette smoking were differentially associated with total and differential WBC counts and IL-6 levels. CONCLUSIONS: Positive in vivo associations of total WBC and its specific subpopulations were identified, including neutrophils, monocytes, and eosinophils, with circulating IL-6 levels in community-dwelling older women. These findings suggest significant contributions of WBC and its subpopulations to circulating IL-6 levels and potential effects from chronic elevation of IL-6 levels to the function of these circulating immune cells that warrant further investigation.

Age Factors↗

PubMed2005

IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer.

Experimental and observational studies in humans and animals suggest that insulin-like growth factor 1 (IGF1) and its principal binding protein, IGFBP3, may influence breast cancer susceptibility. We have examined the association of nine and four single nucleotide polymorphisms (SNPs) in the IGF1 gene and in the IGFBP3 genes, respectively, with circulating levels of their gene products in a population-based study of 600 middle-aged men and women, and in a breast cancer case-control study, comprised 4647 cases and 4564 controls. All study participants are from the East Anglian region of UK. SNPs were specifically chosen to tag all other known SNPs in each gene. Several SNPs in each gene are associated both with circulating levels of their respective proteins and with risk of breast cancer. In particular, the c allele of IGF1 SNPrs1520220 is associated with increased circulating IGF1 (r2=2.1%, P-trend=0.003) in females and an increased risk of breast cancer: odds ratio (OR) (cc/gg)=1.41; 95% confidence intervals (95% CI) 1.11-1.79, P-trend=0.03. The a allele of IGFBP3 SNP rs2854744 is associated with increased circulating IGFBP3 (r2=9.7%, P<10(-9)) and a decreased risk of breast cancer: OR (aa/cc)=0.87; 95% CI 0.77-0.99, P=0.03. Our data indicate that common variants in the IGF1 and IGFBP3 genes are associated with differences in circulating levels of IGF1 and IGFBP3 and with breast cancer risk. More specifically and consistent with experimental models, our data suggest that higher IGF1 levels may increase the risk of breast cancer but higher IGFBP3 levels may be protective.

Breast Neoplasms↗

PubMed1994

Contribution of the fetal adrenal to circulating immunoactive inhibin in the chicken embryo.

High concentrations of immunoactive inhibin are observed in the plasma of male and female chicken embryos. The exact nature and the source of this material remain obscure. In a previous study we presented evidence that the fetal gonads are unlikely to be the main source of circulating inhibin (Biol Reprod 1993; 49:549-554). Here we demonstrate that the fetal adrenal may account for the major portion of circulating immunoactive inhibin in the chicken embryo. A comparison of the inhibin content of different fetal organs shows that, expressed per milligram of tissue, the adrenal ranks second. Only the testis has a higher inhibin content, while the inhibin content of the fetal ovary is considerably lower than that of the fetal adrenal. Suppression of endogenous ACTH secretion by administration of dexamethasone results in a marked decrease of plasma inhibin. Maximal suppression (down to 24% and 25% of the control values in male and female embryos, respectively) was observed with the lowest dose of dexamethasone tested (1 microgram/egg). Dexamethasone (100 microgram/egg) reduced testicular weight and testicular inhibin content to approximately 50% of the control value. It is unlikely, however, that this contributed significantly to the fall in circulating immunoactive inhibin. In fact, ovarian inhibin content was unaffected, but even so, a comparable drop in circulating inhibin was observed in female embryos. Dexamethasone caused only marginal changes in plasma FSH. Administration of a synthetic peptide with ACTH activity (Synacthen) in vivo did not produce measurable changes in circulating inhibin. Isolated and cultured fetal adrenal cells, however, produced immunoactive inhibin, and this production was increased fivefold after stimulation with synthetic ACTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMedDate not supplied

Platelet glycoprotein IIb/IIIa inhibitor attenuates complement activation during in vitro ventricular assist circulation.

Complement activity and platelet glycoprotein (GP) IIb/IIIa dysfunction have been demonstrated during in vitro ventricular assist device circulation. Platelets contain C1 serine protease inhibitor (C1 INH) in secretory granules, which normally regulates complement. Complement activity may result from a loss of platelet regulation on complement during ventricular assist device circulation as platelets lose viability. The purpose of this study was to assess the ability of a platelet GP IIb/IIIa receptor inhibitor to attenuate ventricular assist device associated complement activation during in vitro ventricular assisted circulation. Eight in vitro nonpulsatile centrifugal ventricular assist device circuits were simulated for 4 days using 450 ml fresh human whole blood. Cardiac index, temperature, pH, PO2, PCO2, Ca, glucose, and activated clotting time were maintained at physiologic levels. Levels of C1 INH and C3a were measured with and without a reversible glycoprotein IIb/IIIa inhibitor (MK-383). Concentrations of C1 INH increase on exposure to ventricular assist device, and decrease to a plateau within 12 hr. The decrease in circulating unbound C1 INH was attenuated with pre treatment with MK-383. Concentrations of C3a increase 34 fold within 4 hr of exposure to a ventricular assist device with and 22 fold without pre treatment with MK-383. These findings suggest that protection of the platelet GP IIb/IIIa complex delays complement activation during in vitro ventricular assist device circulation.

Complement Activation↗

PubMedDate not supplied

Protection of platelet glycoprotein IIb/IIIa receptor complex preserves platelet function during in vitro ventricular assisted circulation.

Platelet dysfunction probably contributes to bleeding associated with ventricular assist devices (VADs). Previous evidence suggests that VAD associated platelet dysfunction may be due to dysfunction of the platelet fibrinogen receptor. The purpose of this investigation was to test the hypothesis that selective protection of platelet fibrinogen receptor preserves platelet aggregating ability during in vitro ventricular assisted circulation. Eight in vitro nonpulsatile centrifugal VAD circuits were simulated for four days using 450 ml of fresh human whole blood. Temperature, activated clotting time, pH, PCO2, PO2, Ca2+, and glucose were maintained at physiologic values. Flow was maintained at a constant 2.0 L/min/m2. We examined whole blood platelet aggregation induced by ristocetin, collagen, and adenosine diphosphate (ADP). We added a highly specific reversible inhibitor (MK-383) of the glycoprotein (GP) IIb/IIIa receptor complex before start of circulation to the final four VAD experiments. ADP induced aggregation decreased within the first hour of circulation. Ristocetin and collagen induced aggregation decreased to negligible levels after 10 hours of circulation. With MK-383, ristocetin induced aggregation was preserved. Addition of MK-383 did not alter the decrease of ADP and collagen induced aggregation. These results suggest platelet aggregating ability is maintained with protection of the platelet fibrinogen receptor during in vitro ventricular assisted circulation.

Blood Platelets↗

PubMedDate not supplied

Tirofiban administration attenuates platelet and platelet-neutrophil conjugation but not neutrophil degranulation during in vitro VAD circulation.

Ventricular Assist Devices (VADs) have been used as bridges to heart transplantation. However, VAD circulation is complicated by the incidence of thromboembolism, prolonged bleeding, and activation of the inflammatory cascade. We hypothesize that platelet and neutrophil activation are interrelated and linked to the activation of the glycoprotein (GP) IIb/IIIa platelet receptor. The purpose of this study is to evaluate the effects of Tirofiban, a platelet GP IIb/IIIa receptor inhibitor, on platelet and neutrophil activation during simulated VAD circulation. Two groups of five in vitro VAD circuits were simulated with and without Tirofiban using 450 cc of human blood. Blood samples were drawn at specific time intervals up to 72 hours, measuring leukotriene C4 (LTC4), platelet factor four (PF4), and neutrophil elastase. Tirofiban decreased serum levels of PF4 and LTC4 during VAD circulation. Neutrophil elastase secretion was not affected by Tirofiban administration. Preconditioning of VAD circulation with Tirofiban attenuated platelet activation as demonstrated by a decrease in serum PF4 levels. Tirofiban administration ameliorates the inflammatory response by altering platelet-neutrophil interaction as demonstrated by a decrease in LTC4 production. Continued elastase secretion indicates that the inflammatory response is not completely inhibited by Tirofiban administration. These results suggest that neutrophils may be activated by alternative mechanisms. Early complement activation has been demonstrated during in vivo and in vitro VAD circulation and may play a role in mediating inflammatory and thromboembolic reactions during VAD use.

Blood Platelets↗

PubMed1997

Dose-response relationship between aortic infusions of polymerized bovine hemoglobin and return of circulation in a canine model of ventricular fibrillation and advanced cardiac life support.

OBJECTIVES: Return of spontaneous circulation after cardiac arrest may be a function of vital organ perfusion. Selective aortic perfusion and oxygenation with oxygenated ultrapurified polymerized bovine hemoglobin improves vital organ perfusion and is an effective adjunct in the treatment of cardiac arrest. This study determined the dose-response relationship between intra-aortic oxygenated ultrapurified polymerized bovine hemoglobin and return of spontaneous circulation. DESIGN: Randomized, interventional study, using a clinically relevant model of ventricular fibrillation with a prolonged arrest time and cardiopulmonary resuscitation based on external chest compression and aortic occlusion with oxygenated ultrapurified polymerized bovine hemoglobin infusion. SETTING: University, resuscitation research laboratory. SUBJECTS: Fasted, mongrel dogs (> 20 kg). INTERVENTIONS: After alpha-chloralose anesthesia, blood gases and vital signs were normalized. Electrocardiogram, aortic arch, and intraesophageal pressures were measured continuously. A descending aortic occlusion-infusion balloon catheter was placed through the femoral artery. Ventricular fibrillation was induced and basic life support was begun after 10 mins. Interanimal differences in basic life support were minimized by standardization of the esophageal pulse pressure and aortic blood gases. At 13 mins, the aortic occlusion balloon was inflated and a dose of 10, 20, or 30 mL/kg of ultrapurified polymerized bovine hemoglobin was infused at 300 mL/min. Defibrillation was attempted at the end of the infusion. MEASUREMENTS AND MAIN RESULTS: Only two of five animals given 10 mL/kg of ultrapurified polymerized bovine hemoglobin had return of spontaneous circulation, vs. four of five animals given 20 mL/kg, and all seven animals given 30 mL/kg. All resuscitated animals were alive at 1 hr after return of spontaneous circulation. CONCLUSIONS: There is a dose-response relationship between the volume of oxygenated ultrapurified polymerized bovine hemoglobin administered by selective aortic perfusion and oxygenation and return of spontaneous circulation after prolonged cardiac arrest. This result supports the hypothesis that vital organ flow is causally related to improved outcome.

Animals↗

PubMedDate not supplied

The effects of reduced cerebrovascular circulation on the auditory brain stem response (ABR).

The effect of decreased anterior (carotid) bloodflow on the auditory brain stem response (ABR) was studied in a group of middle-aged males with angiographically confirmed decreased carotid circulation who were candidates for internal carotid end-arterectomy. Individual and mean latencies from the experimental group were compared to latencies of a control group matched for age, sex, and hearing loss. Mean absolute latency of wave V was significantly longer in the group with decreased anterior circulation when compared to the matched control group. These findings are similar to those from studies examining decreased posterior (vertebrobasilar) circulation. Both the matched control and experimental group were also compared to clinic norms and judged for abnormality. None of the control group ABRs were judged abnormal, after correction for hearing loss, while 29% of the ABRs were judged abnormal from the group with decreased anterior circulation. Postoperative testing was performed 1 week after surgery to determine any immediate effects of revascularization of the ABR. No changes in absolute or interpeak latencies were observed for either ear between pre- and postoperative testing. It is concluded that patients with confirmed decreased cerebrovascular circulation may show prolongation of absolute latency of wave V on ABR testing. Revascularization surgery in these patients appears to have no affect on their ABR within 1 week of surgery.

Adult↗

PubMed2002

Effects of chronic hypoxia on the circulating and pancreatic renin-angiotensin system.

INTRODUCTION: The circulating renin-angiotensin system (RAS) plays a crucial role in the regulation of blood pressure, electrolytes, and fluid homeostasis. In contrast to the circulating RAS, the presence of an intrinsic RAS has been demonstrated in different tissues/organs, which may affect both local and global functions of a biologic system. Our previous studies provided solid evidence of the existence of a local RAS in rat pancreas. Our further investigation showed that such a pancreatic RAS could be activated by experimental models of chronic hypoxia and chemically induced pancreatitis. These previous findings formed the basis for the current study. METHODOLOGY: Adult Sprague-Dawley rats were exposed to isobaric hypoxia (10% O2), and the effects on the circulating and pancreatic RAS were documented. RESULTS: The current study shows that exposure of rats to isobaric hypoxia caused a time-dependent increase in plasma renin activity. The activation of circulating RAS by hypoxia was associated with a parallel upregulation of local RAS components, including the mRNA expression of angiotensinogen and angiotensin II receptor types I and II in the pancreas. CONCLUSION: The upregulation of local pancreatic RAS, along with its counterpart circulating RAS, may be responsible for both physiologic and pathophysiologic aspects of a biologic system under chronic hypoxic stress.

Angiotensinogen↗

PubMedDate not supplied

Circulating lymphocyte subsets in major depression and dysthymia with typical or atypical features.

OBJECTIVE: Inconsistent results have been reported concerning circulating lymphocyte subsets in depression. To establish whether the immune alterations in depression could be related to neurovegetative symptoms, lymphocyte subsets were assessed in major depressive and dysthymic patients who exhibited either typical or atypical features (ie, the latter characterized by mood reactivity and reversed neurovegetative features). METHOD: Blood was collected from major depressive, atypical depressive, typical dysthymic, or atypical dysthymic patients and from nondepressed control subjects. Circulating lymphocyte subsets (CD3, CD4, CD8, CD19, CD16/CD56) were determined by flow cytometry. In a subset of patients, lymphocyte subsets were also determined after a 12-week course of antidepressant medication. RESULTS: Although T and B cell populations did not differ between the depressive subtypes and control subjects, circulating natural killer (NK) cells were elevated in depressive illness, and varied as a function of depressive subtype and sex. Among male patients, NK cells were elevated to a greater extent in typical than in atypical depression, and more so in major depressive than in dysthymic patients. Among female patients, circulating NK cells were lower than in male patients, and only among the typical major depressive patients did NK cells exceed those of controls. Normalization of NK cells occurred with successful pharmacotherapy. CONCLUSIONS: Depression may be associated with elevated levels of circulating NK cells. Although the neurovegetative features associated with depression, particularly altered eating, may have contributed to the elevated NK cells, depressive affect itself also contributed in this respect. However, the relative contributions of these factors varied between male and female patients.

Adult↗

PubMed1982

Association of a better kidney graft survival with the presence of circulating immune complexes before transplantation.

The presence of circulating immune complexes was investigated using the C1q-binding assay before and after kidney transplantation in 48 patients with renal failure. Circulating immune complexes were found in 54% of the patients. The presence of circulating immune complexes prior to grafting was associated with a better renal graft survival. Median survival time of grafts in patients with circulating immune complexes was more than 18 months as compared with 21/2 months in patients without such complexes. The incidence of circulating immune complexes in patients before transplant could not be related to the renal disease, viral infections, blood transfusions, or serum levels of lymphocytotoxic antibodies, IgG, or IgM.

Antigen-Antibody Complex↗