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Biomedical subjects

A Feinstein

Publications and source records attributed to A Feinstein.

At least 109 records · Page 6Linked to original sources

Passive immunization against progesterone inhibits endometrial sensitization in pseudopregnant mice and has antifertility effects in pregnant mice which are reversible by steroid treatment.

Pregnant mice were injected 32 h post coitum (p.c.) with a monoclonal antibody against progesterone (5.7 or 9.5 nmol immunoglobulin G (IgG)) or 0.9% (w/v) NaCl (controls). Progesterone was injected starting on day 2, 3, 4 or 5 p.c. Progesterone reversed the antifertility effect of the lower dose of antibody when replacement began on day 2, 3 or 4, though the number of implantation sites was reduced when treatment started on day 3 or 4. By day 5 only one of six treated animals remained pregnant, showing that antibody action was reversible only up to day 4. At the higher dose of antibody, exogenous nidatory oestrogen was also required. Pseudopregnant mice were injected 32 h p.c. with this antibody (5.7 nmol IgG) or 0.9% NaCl (controls). At 16.00 h on day 4 p.c., oil was injected into the lumen of one uterine horn and the magnitude of the decidual cell reaction was assessed 72 h later. Injected horns of antibody-treated females did not respond to intraluminal oil, whereas those of control mice increased fivefold in weight. Steroid treatment after the induction stimulus did not promote decidual growth, indicating that passive immunization reduced endometrial sensitivity. The results show that in the event that antibody fails to arrest the development of all embryos, the absence of endometrial sensitization will preclude the initiation of implantation, unless progesterone is given within 48 h of antibody treatment.

Animals↗

Rabbit and rat C-reactive proteins bind apolipoprotein B-containing lipoproteins.

Immobilized rabbit and rat C-reactive protein (CRP) were found to selectively bind apolipoprotein B (apoB)-containing lipoproteins (low density lipoprotein, LDL and very low density lipoprotein, VLDL) from whole serum in a manner similar to that previously reported with human CRP. In acute phase human serum the CRP is in a free form, not complexed with lipoprotein or any other macromolecular ligand, and in acute phase serum from most rabbits fed on a normal diet the rabbit CRP was also free. However, in acute phase serum or heparinized plasma from hypercholesterolemic rabbits part or all of the CRP was found by gel filtration and immunoelectrophoretic techniques to be complexed with beta-VLDL, an abnormal apoB-containing plasma lipoprotein present in these animals. The presence of extent in different serum samples of CRP complexed with lipoprotein correlated closely with the serum apoB concentration. The formation of complexes between native, unaggregated rabbit CRP in solution and apoB-containing lipoproteins was readily demonstrable experimentally both with the isolated proteins and in whole serum. In all cases these interactions were calcium-dependent and inhibitable by free phosphoryl choline. The present findings extend earlier work in man and the rabbit and indicate that among the C-reactive proteins from different species, which are structurally highly conserved, the capacity for selective binding to apoB-containing plasma lipoproteins is also a constant feature. These interactions may therefore be related to the in vivo function of CRP in all species and this function may in turn be relevant to pathological conditions, such as atherosclerosis, in which lipoproteins are important.

Animals↗

Urticaria and fixed drug eruption in a patient treated with griseofulvin.

We report a case of urticaria and fixed drug eruption ( FDE ) caused by griseofulvin. Although griseofulvin-induced urticaria is well documented, FDE secondary to griseofulvin is distinctly uncommon. Moreover, the appearance of urticaria and FDE in the same patient following treatment with griseofulvin is, we believe, the first to be described in the literature. The concept of FDE is briefly reviewed.

Adult↗

Stub thumbs in Israel revisited.

A three generation family with stub thumbs and short fourth toes is reported. This combination of anomalies has been observed in the past and the question is raised whether this association could be genetically distinct from that of stub thumbs alone.

Adolescent↗

Action of anti-progesterone monoclonal antibody in blocking pregnancy after postcoital administration in mice.

Anti-progesterone monoclonal antibody injected intraperitoneally as a single dose 32 h post coitum completely blocked pregnancy in BALB/c and CBA nulliparous mice. The dose required was greater in CBA than in BALB/c females, but in both strains no implantation sites were detectable at autopsy on day 10 after mating. The action of the antibody in BALB/c females was associated with a failure to initiate an implantation response as indicated by the Pontamine Blue reaction. The most pronounced effect, however, was an arrest of embryonic development at a stage prior to cavitation. Plasma progesterone concentration in blood taken by cardiac puncture was greatly increased after treatment, by virtue of high-affinity binding by antibody in circulation. The results show that passive immunization against progesterone shortly after mating interferes with early hormone-dependent steps which are essential for normal embryonic development.

Animals↗

'Amyloid degrading activity' of human serum, an in vitro clearing effect which does not involve degradation of amyloid fibrils.

Clearing of turbid amyloid A fibril containing agarose gels by human serum has been ascribed to 'amyloid degrading activity'. We report here that this optical phenomenon is not due to an enzymatic reaction, does not involve proteolysis of the fibril subunits and is not inhibited by sera of patients with AA amyloidosis. The extent of clearing correlates closely with the serum albumin concentration and, as previously reported by others, serum albumin itself causes clearing comparable to that of whole serum. Furthermore addition of albumin solutions to turbid aqueous suspensions of AA amyloid fibrils causes immediate clearing. Serum albumin is known to clarify turbid non-amyloid fibril containing gels and is used commercially to improve the optical properties of radial immunodiffusion plates. We therefore propose that this property of albumin, the mechanism of which is not yet understood, underlies the so called 'amyloid degrading activity' of human serum and the latter is not therefore likely to be of in vivo biological or clinical significance.

Amyloid↗

Distinct populations of class II molecules identified by monoclonal antibodies.

Binding inhibition and sequential immunoadsorption studies with two rat monoclonal antibodies have been used to demonstrate the existence of distinct populations (isotypes) of HLA-DR like (class II) molecules in human B lymphoma cell lysates. The structures of the molecules isolated by these two reagents have been compared by peptide 'mapping' and appear to be closely similar.

Antibodies, Monoclonal↗

Steatocystoma multiplex.

A family with a four-generation history of steatocystoma multiplex is presented. The subject described had unusually large tumors on his scalp and forehead which were successfully excised and closed with skin grafts.

Epidermal Cyst↗

Low density lipoprotein and very low density lipoprotein are selectively bound by aggregated C-reactive protein.

C-reactive protein (CRP), the classical acute-phase protein, can bind phospholipids by virtue of its specific, calcium-dependent reactivity with phosphorylcholine residues. However, analysis of acute-phase serum by gel filtration and by density gradient ultracentrifugation showed that the CRP was in a free, uncomplexed form, despite the coexistent presence of the various classes of serum lipoproteins, all of which contain phospholipids. In contrast, when isolated CRP was aggregated by immobilization at a sufficient density on a solid phase and then exposed to normal human serum, it selectively bound low density lipoprotein (LDL) and traces of very low density lipoprotein. The reaction was calcium dependent and reversible by free phosphorylcholine but not by heparin. LDL isolated from normal plasma was also bound by aggregated CRP. CRP reacts in vitro with a wide variety of different ligands both of extrinsic and of autogenous origin, e.g., microbial products and damaged cell membranes, respectively. If CRP aggregated in vivo by complexing with these ligands than acquires the capacity to selectively bind LDL, the phenomenon may have significant implications for the function of CRP and for the metabolism, clearance, and deposition of LDL.

Acute Disease↗

C-reactive protein and serum amyloid P component in the plaice (Pleuronectes platessa L.), a marine teleost, are homologous with their human counterparts.

C-reactive protein and serum amyloid P component were isolated from serum of the plaice (Pleuronectes platessa L.), a murine teleost. The isolation was based on their calcium-dependent binding affinity for pneumococcal C-polysaccharide and for agarose, respectively. These specificities are the same as those of human C-reactive protein and serum amyloid P component, respectively, and we have previously reported that the plaice molecules resemble human C-reactive protein and serum amyloid P component in their electron microscopic appearance. We describe here estimation of the molecular weights of plaice C-reactive protein and serum amyloid P component and their subunits, and analysis of their amino acid composition, glycosylation and partial amino-terminal amino acid sequences. The results establish that plaice C-reactive protein and serum amyloid P component are homologous with each other and with their human counterparts and indicate that there has been stable conservation of this protein family throughout vertebrate evolution.

Amino Acid Sequence↗

Calcium-dependent aggregation of human serum amyloid P component.

Normal human serum or isolated human amyloid P component was ultracentrifuged on density gradients containing either 10 mM EDTA or different concentrations of Ca2+ between 0.15 and 2.15 mM. In the presence of Ca2+ concentrations of 1 mM or more human P component sedimented more rapidly than it did in the presence of lower Ca2+ levels or of EDTA. This phenomenon was due to Ca2+-dependent aggregation of P component molecules and did not require the presence of any other serum constituents. It was completely inhibited by incorporating a physiological concentration (40 mg/ml) of serum albumin in the gradients, suggesting that free ionized Ca2+ is required to promote aggregation of the P component. P component from the mouse and the plaice (Pleuronectes platessa L.), a marine teleost, did not undergo the same Ca2+-dependent aggregation as human P component. These observations resolve a discrepancy existing in the literature concerning the sedimentation rate of human P component in density gradient ultracentrifugation and shed new light on its behaviour with respect to Ca2+ which may be relevant to the deposition of P component in amyloidosis.

Amyloid↗

Isolation and characterization of C-reactive protein and serum amyloid P component in the rat.

C-reactive protein (RP) and serum amyloid P component (SAP) have been identified for the first time in rat serum and isolated by calcium-dependent affinity chromatography. Rat CRP closely resembled human CRP in its amino acid composition, in having five subunits per molecule and in its electron microscopic appearance as a pentameric annular disc. It differed, however, from all other mammalian CRP's characterised hitherto in being a glycoprotein bearing a single complex oligosaccharide on each polypeptide subunit. Furthermore one pair of tis subunits per molecule was linked by a interchain disulphide bridges whereas in other animals the subunits of both CRP and SAP are all non-covalently associated. The serum concentration of CRP in normal healthy laboratory rats and in specific pathogen-free rats was 300-600 micrograms/ml which is much greater than has been described in any other species and exceeds even maximal acute phase levels of CRP in man. Following injections of casein or croton oil, serum CRP levels rose to a maximum of about 900 micrograms/ml. Rat CRP bound to pneumococcal C-polysaccharide (CPS( but, in marked contrast to the behaviour of CRP from man, rabbit and marine teleost fish, it did not precipitate with CPS solutions, agglutinate CPS-coated sheep erythrocytes or initiate complement activation. Rat SAP, like SAP of other species, was a glycoprotein but unlike them it was composed only of a single pentameric disc not two such discs interacting face-to-face. The normal level of SAP in rat serum was 20-50 micrograms/ml, very similar to the levels seen in man, and it did not behave as an acute phase reactant in response to casein or croton-oil injections. In this respect it resembled human SAP but differed from murine SAP which is a major acute phase reactant.

Amino Acids↗