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Biomedical subjects

I Rubin

Publications and source records attributed to I Rubin.

At least 19 recordsLinked to original sources
PubMed2006

Ethics and pharmaceutical medicine -- the full report of the Ethical Issues Committee of the Faculty of Pharmaceutical Medicine of the Royal Colleges of Physicians of the UK.

The practice of pharmaceutical medicine brings with it ethical challenges and dilemmas often very different from those encountered in the practice of clinical medicine. Having established a framework of guiding ethical principles, this report aims to look in some detail at specific areas of possible ethical concern to pharmaceutical physicians, offering practical advice and guidance on good practice. The report covers issues related to pharmaceutical research, including dissemination of research findings, communication with other health professionals and patients and involvement of pharmaceutical physicians and companies in the provision of patient services. The primacy of the interests of patients and the wider public is emphasised, and the possible impact of new developments in pharmaceutical technology is explored. It is hoped that the report will help those working in pharmaceutical medicine and act as a stimulus for wider discussion and debate.

Biomedical Research↗
PubMed2006

Guiding Principles for Pharmaceutical Physicians from the Ethical Issues Committee of the Faculty of Pharmaceutical Medicine of the Royal Colleges of Physicians of the UK.

Medical practitioners practising in the field of pharmaceutical medicine, whether in industry, regulatory bodies or an academic environment, are bound by the same ethical standards which apply to all doctors. Their work, however, leads to some very specific ethical considerations which may not be fully explored in ethical codes based in clinical medicine. This document aims to establish some guiding principles which should underpin a working ethical framework for pharmaceutical physicians. It clearly places the protection of patients (and research subjects) and the doctor's duties to wider society ahead of responsibilities to an individual employer while emphasising the importance of adherence to high standards of research, including dissemination of findings. These principles form the basis of a fuller report which offers more specific practical advice on possible ethical conflicts or dilemmas.

Clinical Trials as Topic↗
PubMed2004

Nitric oxide synthase expression and enzymatic activity in multiple sclerosis.

We used post-mortem magnetic resonance imaging (MRI) guidance to obtain paired biopsies from the brains of four patients with clinical definite multiple sclerosis (MS). Samples were analyzed for the immunoreactivity (IR) of the three nitric oxide (NO) synthase isoforms [inducible, neuronal and endothelial nitric oxide synthase (NOS)], and enzymatic NO synthase activity. MRI guided biopsies documented more active plaques than macroscopic examination, and histological examination revealed further lesions. Inducible NOS (iNOS) was the dominant IR isoform, while reactive astrocytes were the dominant iNOS expressing cells in active lesions. NOS IR expressing cells were widely distributed in plaques, in white and gray matter that appeared normal macroscopically, and on MR. Endothelial NOS (eNOS) was highly expressed in intraparenchymal vascular endothelial cells of MS patients. A control group matched for age and sex showed no such changes. Our data support the hypothesis that NO is a pathogenic factor in MS, and that NOS IR is strongly expressed in brain regions appearing normal by MRI.

Adult↗
PubMed2002

Nitric oxide synthase activity in human pituitary adenomas.

OBJECTIVES: The purpose of the present study was to examine human pituitary adenomas for nitric oxide synthase (NOS) activity by immunohistochemical and enzymatic methods. MATERIALS AND METHODS: Adenomatous tissue from 16 patients were obtained during operation and stained immunohistochemically for hormone production and for the three NOS isoenzymes. Cell types that expressed NOS immunoreactivity (IR) were identified, and the NOS isoform was noted. NOS activity was measured enzymatically by the conversion of L-arginine to L-citrulline in tissue samples. RESULTS: Endothelial cells of pituitary adenomas showed increase of eNOS IR compared with control tissue. The nNOS and iNOS IR were the same in adenomas and controls. There was no correlation between NOS IR and NOS activity measured enzymatically and the endocrine activity of the tumour or other clinical variables. CONCLUSION: The observation of increased eNOS IR in endothelial cells of adenomas may suggest that NO plays a role in the regulation of blood flow in pituitary adenomas.

Adenoma↗
PubMed2001

Endothelium-dependent vasorelaxation in inhibited by in vivo depletion of vascular thiol levels: role of endothelial nitric oxide synthase.

Thiols like glutathione may serve as reducing cofactors in the production of nitric oxide (NO) and protect NO from inactivation by radical oxygen species. Depletion of thiol compounds reduces NO-mediated vascular effects in vitro and in vivo. The mechanisms underlying these actions are not clear, but may involve decreased synthesis of NO and/or increased degradation of NO. This study investigates the effect of glutathione depletion on the response to NO-mediated vasodilation induced by acetylcholine (Ach, 10 micrograms/kg), endothelial NO synthase (eNOS) activity and potential markers of vascular superoxide anion (O2.-) production in conscious chronically catheterized rats. Thiol depletion induced by buthionine sulfoximine (BSO, 1 g i.p. within 24 h) decreased the hypotensive effect of Ach by 30% (MAP reduction before BSO 27 +/- 3 mmHg, 19 +/- 3 mmHg after BSO, (mean +/- SEM), p < .05, n = 8). The impaired effect of Ach was associated with a significant reduction in eNOS activity (control: 7.7 +/- 0.8, BSO: 3.9 +/- 0.4 pmol/min/mg protein (p < .05), n = 6). In contrast, neither NADH/NADPH driven membrane-associated oxidases nor lucigenin reductase activity were significantly (p < .05) affected by BSO (BSO: 4415 +/- 123, control: 4105 +/- 455 counts/mg; n = 6) in rat aorta. It is concluded that in vivo thiol depletion results in endothelial dysfunction and a reduced receptor-mediated vascular relaxation. This effect is caused by reduced endothelial NO formation.

Acetylcholine↗
PubMed2001

The basic biology of HER2.

Human epidermal growth factor receptors (HER/erbB) constitute a family of four cell surface receptors involved in transmission of signals controlling normal cell growth and differentiation. A range of growth factors serve as ligands, but none is specific for the HER2 receptor. HER receptors exist as both monomers and dimers, either homo- or heterodimers. Ligand binding to HERI, HER3 or HER4 induces rapid receptor dimerization, with a marked preference for HER2 as a dimer partner. Moreover, HER2-containing heterodimers generate intracellular signals that are significantly stronger than signals emanating from other HER combinations. In normal cells, few HER2 molecules exist at the cell surface, so few heterodimers are formed and growth signals are relatively weak and controllable. When HER2 is overexpressed multiple HER2 heterodimers are formed and cell signaling is stronger, resulting in enhanced responsiveness to growth factors and malignant growth. This explains why HER2 overexpression is an indicator of poor prognosis in breast tumors and may be predictive of response to treatment. HER2 is a highly specific and promising target for new breast cancer treatments. The recombinant human anti-HER2 monoclonal antibody (rhuMAb-HER2, trastuzumab, Herceptin) induces rapid removal of HER2 from the cell surface, thereby reducing its availability to heterodimers and reducing oncogenicity.

Animals↗
PubMed2001

The complete human olfactory subgenome.

Olfactory receptors likely constitute the largest gene superfamily in the vertebrate genome. Here we present the nearly complete human olfactory subgenome elucidated by mining the genome draft with gene discovery algorithms. Over 900 olfactory receptor genes and pseudogenes (ORs) were identified, two-thirds of which were not annotated previously. The number of extrapolated ORs is in good agreement with previous theoretical predictions. The sequence of at least 63% of the ORs is disrupted by what appears to be a random process of pseudogene formation. ORs constitute 17 gene families, 4 of which contain more than 100 members each. "Fish-like" Class I ORs, previously considered a relic in higher tetrapods, constitute as much as 10% of the human repertoire, all in one large cluster on chromosome 11. Their lower pseudogene fraction suggests a functional significance. ORs are disposed on all human chromosomes except 20 and Y, and nearly 80% are found in clusters of 6-138 genes. A novel comparative cluster analysis was used to trace the evolutionary path that may have led to OR proliferation and diversification throughout the genome. The results of this analysis suggest the following genome expansion history: first, the generation of a "tetrapod-specific" Class II OR cluster on chromosome 11 by local duplication, then a single-step duplication of this cluster to chromosome 1, and finally an avalanche of duplication events out of chromosome 1 to most other chromosomes. The results of the data mining and characterization of ORs can be accessed at the Human Olfactory Receptor Data Exploratorium Web site (http://bioinfo.weizmann.ac.il/HORDE).

Chromosome Mapping↗
PubMed2000

Nitric oxide synthase activity and expression in experimental diabetic neuropathy.

The changes of nitric oxide synthase (NOS) activity and expression in experimental diabetic neuropathy have not been examined. Increases in ganglia NOS might be similar to those that follow axotomy, whereas declines in endothelial NOS (eNOS) and immunological NOS (iNOS) might explain dysfunction of microvessels or macrophages. In this work, we studied NOS activity in lumbar dorsal root ganglia (DRG) of rats with both short- and long-term experimental streptozotocin-induced diabetes and correlated it with expression of each of the 3 NOS isoforms. NOS enzymatic activity in DRG increased after 12 months of diabetes. This increase, however, was not accompanied by an increase in neuronal NOS immunohistochemistry or mRNA. Immunohistochemical and RT-PCR studies did not identify changes of eNOS expression in 12-month sciatic nerves or DRG from diabetics. Two-month diabetic DRG had increased eNOS mRNA and there was novel eNOS labeling of capsular DRG and perineurial cells. iNOS mRNA levels were lower in diabetics at both time points in peripheral nerves but were unchanged in DRG. Diabetic ganglia showed an increase in NOS activity not explained by novel NOS isoform synthesis. The increases may compensate for NO "quenching" by endproducts of glycosylation. Declines in iNOS may indicate impaired macrophage function.

Animals↗
PubMed2000

In vivo mechanisms of acetylcholine-induced vasodilation in rat sciatic nerve.

We examined the importance of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), and neurogenic activity in agonist-induced vasodilation and baseline blood flow [i.e., nerve microvascular conductance (NMVC)] in rat sciatic nerve using laser Doppler flowmetry. Agonists were acetylcholine (ACh) and 3-morpholinosydnonimine (SIN-1). Vasodilation occurring despite NO synthase (NOS) and cyclooxygenase inhibition and showing dependence on K(+) channel activity was taken as being mediated by EDHF. NOS and cyclooxygenase inhibition with N(omega)-nitro-L-arginine (L-NNA) + indomethacin (Indo) revealed two phases of ACh-induced vasodilation: an initial, transient L-NNA + Indo-resistant vasodilation, peaking at 23 +/- 6 s and lasting 145 +/- 69 s, followed by sustained L-NNA + Indo-sensitive vasodilation. L-NNA alone did not affect sustained ACh-induced vasodilation but decreased baseline NMVC by 55%. In the presence of L-NNA + Indo, the K(+) channel blocker tetraethylammonium (TEA) inhibited transient ACh-induced vasodilation by 58% and reduced baseline NMVC by 25%. SIN-1-induced vasodilation increased fourfold in the presence of L-NNA, whereas the specific guanylyl cyclase inhibitor 1H-(1, 2, 4)oxadiazolo(4,3-alpha)quinoxalin-1-one abolished it. However, in homogenates of rat sciatic nerve, SIN-1-stimulated soluble guanylyl cyclase (sGC) activity was unaffected by L-NNA. TTX affected neither SIN-1- nor ACh-induced vasodilation. In conclusion, ACh-induced vasodilation consisted of two components, the first partially mediated by EDHF and the second by a vasodilatory prostanoid + NO. Baseline NMVC was dependent on NO and EDHF. Although L-NNA enhanced SIN-1-induced vasodilation, it had no effect on sGC-activity.

Acetylcholine↗
PubMed1999

Evidence for nitric oxide and nitric oxide synthase activity in proximal stumps of transected peripheral nerves.

Nitric oxide may be liberated as an inflammatory mediator within injured peripheral nerve trunks. We evaluated the proximal stumps of injured peripheral nerve stumps that later form neuromas or regenerative nerve sprouts, for evidence of local nitric oxide elaboration and activity. Proximal stumps were created in male Sprague-Dawley rats by sectioning of the sciatic nerve and resection of its distal portions and branches. There was striking physiological evidence of nitric oxide activity at the tips of 48-h and 14-day-old proximal nerve stumps. We detected local nitric oxide-mediated hyperemia of both extrinsic plexus and endoneurial microvessels that was reversible, in a dose-dependent stereospecific fashion, by the broad-spectrum nitric oxide synthase inhibitors, Nomega-nitro-L-arginine-methyl ester or Nomega-nitro-L-arginine, but not by 7-nitroindazole, an inhibitor with relative selectivity for neuronal nitric oxide. Immunohistochemical studies provided evidence for the localization of nitric oxide generators at the same sites. In 48-h but not 14-day stumps increased expression of two isoforms of nitric oxide synthase was detected: endothelial nitric oxide and to a much lesser extent neuronal nitric oxide synthase. Both isoforms appeared in axonal endbulb-like profiles that co-localized with neurofilament immunostaining. Western immunoblots identified a band consistent with endothelial nitric oxide synthase expression. In 14-day stumps with early neuroma formation, but not 48-h stumps, there was staining for immunological nitric oxide synthase in some endoneurial and epineurial macrophages. Total nitric oxide synthase biochemical enzymatic activity, measured by labelled arginine to citrulline conversion, was increased in 14-day but not 48-h stumps. Injured peripheral nerves have evidence of early nitric oxide action, nitric oxide synthase expression and nitric oxide activity in proximal nerve stumps. Nitric oxide may have an important impact on the regenerative milieu.

Animals↗
PubMed1998

Nitric oxide scavenging by hemoglobin or nitric oxide synthase inhibition by N-nitro-L-arginine induces cortical spreading ischemia when K+ is increased in the subarachnoid space.

We investigated the combined effect of increased brain topical K+ concentration and reduction of the nitric oxide (NO.) level caused by nitric oxide scavenging or nitric oxide synthase (NOS) inhibition on regional cerebral blood flow and subarachnoid direct current (DC) potential. Using thiopental-anesthetized male Wistar rats with a closed cranial window preparation, brain topical superfusion of a combination of the NO. scavenger hemoglobin (Hb; 2 mmol/L) and increased K+ concentration in the artificial cerebrospinal fluid ([K+]ACSF) at 35 mmol/L led to sudden spontaneous transient ischemic events with a decrease of CBF to 14+/-7% (n=4) compared with the baseline (100%). The ischemic events lasted for 53+/-17 minutes and were associated with a negative subarachnoid DC shift of -7.3+/-0.6 mV of 49+/-12 minutes' duration. The combination of the NOS inhibitor N-nitro-L-arginine (L-NA, 1 mmol/L) with [K+]ACSF at 35 mmol/L caused similar spontaneous transient ischemic events in 13 rats. When cortical spreading depression was induced by KCl at a 5-mm distance, a typical cortical spreading hyperemia (CSH) and negative DC shift were measured at the closed cranial window during brain topical superfusion with either physiologic artificial CSF (n=5), or artificial CSF containing increased [K+]ACSF at 20 mmol/L (n=4), [K+]ACSF at 3 mmol/L combined with L-NA (n=10), [K+]ACSF at 10 mmol/L combined with L-NA (five of six animals) or [K+]ACSF at 3 mmol/L combined with Hb (three of four animals). Cortical spreading depression induced longlasting transient ischemia instead of CSH, when brain was superfused with either [K+]ACSF at 20 mmol/L combined with Hb (CBF decrease to 20+/-20% duration 25+/-21 minutes, n=4), or [K+]ACSF at 20 mmol/L combined with L-NA (n=19). Transient ischemia induced by NOS inhibition and [K],ACSF at 20 mmol/L propagated at a speed of 3.4+/-0.6 mm/min, indicating cortical spreading ischemia (CSI). Although CSH did not change oxygen free radical production, as measured on-line by in vivo lucigenin-enhanced chemiluminescence, CSI resulted in the typical radical production pattern of ischemia and reperfusion suggestive of brain damage (n=4). Nimodipine (2 microg/kg body weight/min intravenously) transformed CSI back to CSH (n=4). Vehicle had no effect on CSI (n=4). Our data suggest that the combination of decreased NO. levels and increased subarachnoid K+ levels induces spreading depression with acute ischemic CBF response. Thus, a disturbed coupling of metabolism and CBF can cause ischemia. We speculate that CSI may be related to delayed ischemic deficits after subarachnoid hemorrhage, a clinical condition in which the release of Hb and K+ from erythrocytes creates a microenvironment similar to the one investigated here.

Animals↗
PubMed1997

Laminar analysis of activity-dependent increases of CBF in rat cerebellar cortex: dependence on synaptic strength.

The purpose of the present study was to examine mechanisms of activity-dependent changes of cerebral blood flow (CBF) in rat cerebellar cortex by laser-Doppler flowmetry, using two synaptic inputs that excite different regions of the same target cell and with different synaptic strength. The apical part of Purkinje cells was activated by electrical stimulation of parallel fibers, whereas the cell soma and the proximal part of the dendritic tree were activated by climbing fibers using harmaline (40 mg/kg ip) or electrical stimulation of the inferior olive. Glass microelectrodes were used for recordings of field potentials and single-unit activity of Purkinje cells. CBF increases evoked by parallel fibers were most pronounced in the upper cortical layers. In contrast, climbing fiber stimulation increased CBF in the entire cortex. Inhibition of nitric oxide (NO) synthase activity by NG-nitro-L-arginine (L-NNA) or guanylate cyclase activity by 1H-[1,2,4(oxadiazolo)4,3-a]quinoxaline-1-one did not affect basal or harmaline-induced Purkinje cell activity but attenuated harmaline- and parallel fiber-evoked CBF increases by approximately 40-50%. Application of 8-(p-sulfophenyl)theophylline and adenosine deaminase reduced the harmaline-evoked CBF increase without any effect on the parallel fiber-evoked CBF response. The results suggest that CBF increases elicited by activation of Purkinje cells are partially mediated by the NO-guanosine 3',5'-cyclic monophosphate system independent of the input function but that adenosine contributes as well when climbing fibers are activated. This is the first demonstration of variations of coupling as a function of postsynaptic activity in the same cell.

Analysis of Variance↗
PubMed1996

Role of nitric oxide synthase inhibition in leukocyte-endothelium interaction in the rat pial microvasculature.

We investigated the role of nitric oxide (NO) in leukocyte-endothelium interaction, blood-brain barrier (BBB) function and oxygen free-radical production in the rat pial microcirculation. In a closed cranial window preparation (dura removed) over the parietal cortex of pentobarbital-anesthetized Wistar rats, NO synthase (NOS) was inhibited by systemic and/or topical application of N omega-nitro-L-arginine (L-NNA) under physiological conditions and during leukotriene B4 (LTB4) activation. Circulating leukocytes were labeled by intravenous injection of rhodamine 6G. We used a confocal laser scanning microscope (CLSM) and studied leukocyte rolling and sticking in pial veins and arteries before and after NOS inhibition. At the end of the experiments, sodium-fluorescein was injected intravenously to test BBB integrity. Brain cortex oxygen free-radical production was investigated in the cranial window preparation using lucigenin-enhanced chemiluminescence (CL). L-NNA application did not lead to significant changes in leukocyte-endothelium interaction, BBB function, and oxygen free-radical production under physiological conditions [leukocyte-endothelium interaction: control (n = 5), L-NNA systemically (n = 5), L-NNA topically (n = 5): at baseline rollers/100 microns: 0.76 +/- 0.55, 0.64 +/- 0.94, 0.44 +/- 0.55 and stickers/100 microns: 0.90 +/- 0.28, 0.76 +/- 0.24, 0.84 +/- 0.42; at 60 min rollers/100 microns: 1.49 +/- 0.66, 1.21 +/- 0.99, 0.67 +/- 0.66 and stickers/100 microns: 1.04 +/- 0.20, 1.19 +/- 0.23, 1.21 +/- 0.54; oxygen free-radical production (n = 4): CL count before L-NNA application 35 +/- 17 cps, after 1 h of topical superfusion of L-NNA 38 +/- 14 cps; p < 0.05]. In contrast to the results achieved under physiological conditions, a significant further increase of rolling leukocytes and BBB permeability occurred due to NOS inhibition under LTB4-activated conditions [76 +/- 47% significant (p < or = 0.01, n = 7) further increase of rollers/100 microns due to 60 min L-NNA application following the activation period of 120 min LTB4 superfusion]. Our results support a modulatory role for NO in leukocyte-endothelium interaction and BBB permeability in the pial microcirculation when this interaction is increased.

Animals↗
PubMed1996

NOS activity in brain and endothelium: relation to hypercapnic rise of cerebral blood flow in rats.

We examined whether attenuation of the hypercapnic increase of cerebral blood flow (CBF) associated with nitric oxide synthase (NOS) inhibition is related to local neuronal or aortic endothelial NOS activity or local endothelial/neuronal NOS-dependent vasodilation. Halothane-anesthetized rats were ventilated, and CBF was measured by laser-Doppler flowmetry over the parietal and cerebellar cortex. Intravenous N omega-nitro-L-arginine (L-NNA; 30 mg/kg) inhibited brain and aortic NOS activity by 67-70%. Topical L-NNA (1 mM) inhibited brain NOS activity by 91-94%, whereas aortic NOS activity remained constant. In contrast, intravenous L-NNA attenuated the hypercapnic CBF rise much more efficiently than topical L-NNA. 7-Nitroindazole, another NOS inhibitor, attenuated endothelial and neuronal NOS activity equally well and inhibited the hypercapnic CBF increase as effectively as L-NNA. Topical L-NNA and 7-nitroindazole abolished local endothelial NOS-dependent vasodilation after 15 min, whereas hypercapnic CBF was only slightly reduced. L-NNA injected into the tissue abolished neuronal NOS-dependent vasodilation, whereas hypercapnic CBF was unchanged. The findings suggest that local NOS activity, whether neuronal or endothelial, is unimportant for the hypercapnic rise of CBF.

Acetylcholine↗
PubMed1996

Elevated des-AngI-angiotensinogen levels by nephrectomy and adrenalectomy.

This study investigates the time course of plasma levels of angiotensinogen (Aogen) and of the Aogen metabolite des-AngI-angiotensiongen (des-AngI-Aogen) in nephrectomized rats with and without adrenals for 24 h. After nephrectomy the plasma Aogen levels increased 5-fold over the following 24 h. The increase is significantly lower after sham nephrectomy (3.7-fold, P < 0.05) and if the kidneys are withdrawn without decapsulization (2.4-fold, P < 0.05). A small and transient increase arise after nephrectomy plus adrenalectomy (1.6-fold after 8 h, P < 0.005). After adrenalectomy alone Aogen levels continuously shrink to 38% of control values after 24 h. Plasma des-AngI-Aogen levels increase 2.1- to 3.7-fold 24 h after the different nephrectomy procedures. In connection with recent findings these data support the notion that the increase in Aogen plasma levels after bilateral nephrectomy is triggered by renin, released during surgery. High plasma levels of des-AngI-Aogen after nephrectomy indicate that AngI is generated by tissue renin, e.g., in the adrenals. This suggests that after nephrectomy the plasma des-AngI-Aogen levels should be a valuable proof for the evaluation of the amount of generated angiotensin.

Adrenalectomy↗
PubMed1996

Learning how to learn: the key to CQI.

All CQI/TQM efforts share a common purpose: to learn something that can correct past mistakes and/or to create better futures. Because learning is a dynamic circular process, the information about a problem or an opportunity will be limited unless four perceptions of the truth--each valid, and each incomplete--are accepted. These four types of learning styles or ways of perceiving are: abstract conceptualizers, active experimenters, concrete experiencers, and reflective observers. Unless all the stages of the learning process have been fully completed, unless all the strokes work in harmony, we cannot be confident that a CQI effort has added its full value. A CQI team's interpersonal process, the tools by which individually limited truths are forged into a consensual holistic truth, must ensure that the group's effort goes "around in circles."

Education, Continuing↗
PubMed1995

Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma.

In sera from pregnant women, pregnancy-associated plasma protein-A (PAPP-A) circulates as a disulfide-bound complex (approximately 474 kDa) with the proform of eosinophil major basic protein (proMBP) (Oxvig, C., Sand, O., Kristensen, T., Gleich, G. J., and Sottrup-Jensen, L. (1993) J. Biol. Chem. 268, 12243-12246). We have produced monoclonal antibodies (mAbs) against the PAPP-A.proMBP complex and established a radioimmunoassay utilizing a mAb recognizing the PAPP-A subunit. Surprisingly, serum levels of proMBP exceed those of PAPP-A four to 10-fold on a molar basis throughout pregnancy. This result prompted an investigation of the status of proMBP in pregnancy. Using a proMBP-specific mAb two novel proMBP complexes have been isolated by chromatographic techniques. Based on sequence analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and reaction with specific antibodies, one is shown to be a 2:2 disulfide-bound complex (approximately 200 kDa) between proMBP and angiotensinogen. The other is a 2:2:2 complex (approximately 300 kDa) between proMBP, angiotensinogen, and complement C3dg. Circulating proMBP in pregnancy is thus present in three types of complexes. These results suggest that specific interactions between the complexed proteins occur in pregnancy, and the possibility is raised that their interactions are important in the pathophysiology of pregnancies associated with hypertension.

Amino Acid Sequence↗