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Biomedical subjects

S S Shapiro

Publications and source records attributed to S S Shapiro.

At least 73 records · Page 4Linked to original sources
PubMed1988

The natural history of factor VIII:C inhibitors in patients with hemophilia A: a national cooperative study. II. Observations on the initial development of factor VIII:C inhibitors.

During a 4-year multicenter cooperative study of acquired factor VIII inhibitors in persons with hemophilia A, new inhibitors were detected in 31 of 1,306 patients who entered the study without an inhibitor or the history of an inhibitor. The incidence of new inhibitors was eight per 1,000 patient-years of observation. The factor VIII:C level before inhibitor development was less than or equal to 0.03 U/mL in 29 individuals and 0.06 U/mL and 0.07 U/mL in the remaining two. Factor VIII:Ag levels were measured in 27 individuals and were less than 0.03 U/mL in 23 and 0.05 to 0.11 U/mL in the remaining four. Maximum inhibitor levels ranged from 1.0 to 9,044 Bethesda U/mL. In seven patients under the age of 20, relatively weak inhibitors (none higher than 4.3 Bethesda U/mL) were detected on only a single occasion despite continued factor VIII challenge. In the other 24 patients with inhibitors detected on multiple occasions, 50% had appeared by age 20 and 71% by age 30. Seventeen of the 31 inhibitors, including 12 of 15 with maximum values greater than 10 Bethesda U/mL, developed within 75 exposure days to factor VIII.

Age Factors↗
PubMed1988

Cultured human umbilical vein endothelial cells contain a membrane glycoprotein immunologically related to platelet glycoprotein Ib.

Using a platelet glycoprotein Ib (GpIb)-specific monoclonal antibody, AP-1, we have studied cultured human umbilical vein endothelial cells (HUVEC) for the presence of GpIb. Radiolabeled AP-1 bound specifically and saturably to HUVEC in suspension and detected a single class of binding sites (100,000/cell). When Triton X-100 extracts of HUVEC were chromatographed on wheat germ agglutinin (WGA)-Sepharose, radioiodinated, precipitated with AP-1, and subjected to reduced sodium dodecyl sulfate-polyacrylamide electrophoresis (SDS-PAGE), major radioactive bands of 228,000, 145,000, and 130,000 were seen. The latter two bands correspond to the 156,000 and 140,000 bands, representing GpIb alpha and glycocalicin, respectively, which are seen when platelets are subjected to the same procedure. The 228,000 band corresponds to a band previously noted in immunoprecipitates of platelet GpIb but not fully explained. When HUVEC were grown in the presence of 35S-methionine, extracted with Triton X-100, chromatographed on WGA-Sepharose, immunoprecipitated with AP-1, and subjected to reduced SDS-PAGE, radioactive bands of 210,000, 156,000, and 90,000 were seen. We conclude that cultured HUVEC synthesize and express on their surface a glycoprotein immunologically related to platelet GpIb.

Antibodies, Monoclonal↗
PubMed1987

A human erythroleukemia cell line synthesizes a functionally active glycoprotein IIb-IIIa complex capable of binding fibrinogen.

The human erythroleukemia (HEL) cell line is known to express a number of platelet-megakaryocyte markers, including glycoproteins IIb and IIIa. Using [35S]methionine as well as monoclonal and polyclonal antibodies to glycoprotein IIb and IIIa, we have demonstrated synthesis of these two glycoproteins by this cell line. When Triton X-100-solubilized membranes were subjected to cross immunoelectrophoresis in 1% agarose, using a mixture of polyclonal antibodies to glycoproteins IIb and IIIa, a single peak was seen in the presence of Ca2+, whereas two distinct peaks were seen in the presence of 5 mM EDTA. When these crossed immunoelectrophoresis were overlaid with 125I-labelled fibrinogen, binding of fibrinogen to the glycoprotein IIb and IIIa complex peak was observed. When either the electrophoresis or the subsequent overlay was done in the presence of 5 mM EDTA, no 125I-fibrinogen binding was observed. These studies demonstrate that HEL cells contain glycoproteins IIb and IIIa capable of forming a Ca2+-dependent complex and capable of binding fibrinogen in a Ca2+-dependent reaction. Nevertheless, glycoprotein IIb- and IIIa-specific fibrinogen binding, of the type observed in platelets, could not be demonstrated in 'resting' or 'stimulated' intact HEL cells. The mechanism giving rise to this difference is currently unknown.

Antibodies↗
PubMed1987

Immunological specificity and mechanism of action of IgG lupus anticoagulants.

Although observations have implied that lupus anticoagulants have immunologic specificity toward anionic phospholipids, this assumption has been directly demonstrated in only one patient with a monoclonal IgM paraprotein. We tested the generality of this hypothesis directly by isolating five IgG lupus anticoagulants from patients with lupuslike syndromes and/or thrombosis. IgG lupus anticoagulant fractions were isolated free of other plasma proteins and free of contaminating phospholipid by adsorption to and elution from cardiolipin-cholesterol-dicetyl phosphate liposomes, followed by chromatography on protein A-Sepharose. Cardiolipin liposomes, but not phosphatidylcholine liposomes, were capable of removing all, or nearly all, lupus anticoagulant activity from patient plasma. The affinity-purified IgG preparations reacted with cardiolipin, phosphatidylserine, phosphatidylinositol, and phosphatidic acid, but not with phosphatidylcholine or phosphatidylethanolamine, and inhibited calcium-dependent binding of prothrombin and of factor X to phosphatidylserine-coated and to cardiolipin-coated surfaces. F(ab')2 fragments retained lupus anticoagulant activity and bound to cardiolipin in an enzyme-linked immunosorbent assay (ELISA). Anticardiolipin and lupus anticoagulant activity were both present in acidic fractions on isoelectric focusing. These data strongly suggest that most, if not all, lupus anticoagulants are antibodies that have immunologic specificity towards anionic phospholipids, thereby blocking the calcium-mediated binding of vitamin K-dependent coagulation factors to coagulation-active phospholipid surfaces.

Antibodies↗
PubMed1986

Flurbiprofen for the treatment of primary dysmenorrhea.

Following the demonstration that increased prostaglandin F2 alpha production causes pain similar to dysmenorrhea, and the finding that prostaglandin synthetase inhibitors are capable of relieving menstrual pain, the early theory of uterine ischemia has once again gained support as the most likely explanation for this condition. In a double-blind, placebo-controlled, crossover study, 30 of 43 women with moderate to severe dysmenorrhea who completed the trial preferred flurbiprofen (Ansaid, Upjohn), a potent new analgesic/anti-inflammatory agent (50 mg four times daily), to aspirin (650 mg four times daily) and placebo. Flurbiprofen was also rated superior to aspirin and placebo in the degree of pain relief. An algorithm for the diagnosis and treatment of 90 percent of women with primary dysmenorrhea is presented.

Adolescent↗
PubMed1986

Successful preoperative apheresis of factor VIII antibody using factor VIII concentrate as a replacement fluid.

Plasma exchange was performed on a patient with hemophilia A and inhibitor to factor VIIIC prior to bilateral cataract removal. Koate was used as replacement fluid with effective reduction of the inhibitor level. From the technical standpoint we found out that factor VIII is best reconstituted in water and directly infused through the venous line and not the centrifuge bowl.

Adult↗
PubMed1986

Oxidation as a possible mechanism of cellular aging: vitamin E deficiency causes premature aging and IgG binding to erythrocytes.

Senescent-cell antigen is a "neo-antigen" that appears on the surface of senescent cells and initiates IgG binding and cellular removal. As an approach to evaluating oxidation as a possible mechanism for generation of senescent-cell antigen, we studied erythrocytes from vitamin E-deficient rats. Vitamin E is localized primarily in cellular membranes. Its major role is the termination of free-radical chain reactions propagated by the polyunsaturated fatty acids of membrane propagated by the polyunsaturated fatty acids of membrane phospholipids. Results of our studies indicate that erythrocytes of all ages from vitamin E-deficient rats behave like old erythrocytes from normal rats, as determined by their susceptibility to phagocytosis, IgG binding, anion transport ability, and glyceraldehyde-3-phosphate dehydrogenase activity. Increased breakdown products of band 3 were observed with immunoblotting in membranes of erythrocytes from vitamin E-deficient rats. Breakdown products of band 3 are known to increase as cells age in normal individuals. The data suggest that oxidation may be a possible mechanism for erythrocyte aging and generation of senescent-cell antigen in vivo.

Anemia, Hemolytic↗
PubMed1986

Effect of beta-carotene and canthaxanthin on the immune responses of the rat.

Male Wistar Kyoto rats were fed diets containing either 2 g/kg (0.2%) beta-carotene, canthaxanthin or basal diet for up to 66 wk. Plasma and tissues were analyzed for vitamin A, vitamin E, beta-carotene or canthaxanthin levels. In vitro immune responses of splenocytes to T- and B-lymphocyte mitogens were determined. T- and B-lymphocyte responses were consistently enhanced in the groups fed beta-carotene or canthaxanthin. Since canthaxanthin cannot be converted to vitamin A, the immunoenhancement seen in these experiments is attributed to a carotenoid effect.

Animals↗
PubMed1986

The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants.

We describe here a test for lupus anticoagulants based on a modified Russell viper venom time (RVVT), using limiting amounts of phospholipid and venom. We have studied 29 patients with a prolonged dilute RVVT. Five of the 29 had a normal activated partial thromboplastin time and three of 14 tested by the tissue thromboplastin inhibition test were normal. In 17 of 19 patients tested, the dilute RVVT was completely normal when ionophore-treated platelets were substituted for phospholipid; the remaining two patients, both with very long phospholipid-dependent dilute RVVT's, were nearly completely normalized. The dilute RVVT is not prolonged in the presence of antibodies to factors VIII, IX, or XI. Thus, the dilute RVVT appears to be a simple, reproducible, sensitive, and relatively specific method for the detection of lupus anticoagulants.

Autoantibodies↗
PubMed1986

Immunoperoxidase localization of prolactin in endometrium during normal menstrual, luteal phase defect, and corrected luteal phase defect cycles.

An avidin-biotin immunoperoxidase staining technique for human prolactin (hPRL) was developed for determination of the location of PRL-producing cells in the endometrium of women with normal menstrual cycles (NMC), luteal phase defects (LPD), and corrected LPD cycles (CLPD). One hundred eight biopsy specimens were studied. Fifty-six patients had NMC, 29 had LPD, and 23 had CLPD. Only decidualized stromal cells stained specifically for hPRL. There was no specific staining in specimens dated earlier than day 25. All specimens dated later than day 25 exhibited decidual cell staining. In specimens dated day 25, 15 of 20 NMC, 5 of 11 CLPD, and 6 of 10 LPD demonstrated decidual staining (P greater than 0.1). These findings suggest that decidual cells are responsible for hPRL production in late secretory endometrium and that the ability of decidual cells to stain for hPRL is dependent on the histologic date of the endometrium and not on the diagnosis of LPD or CLPD.

Bromocriptine↗
PubMed1985

The use of a mobile laboratory cart in a successful university-based human in vitro fertilization program.

The use of a mobile laboratory unit for a successful university-based IVF program is described. The construction of the cart is described in detail. The laboratory cart can be pushed to any site where ovum aspiration is carried out (either operating theater or ultrasound facilities). Aspirated oocytes can be transferred immediately to culture media and transported back to the gamete handling laboratory for embryo culture. Developing embryos can also be transported to any location in the hospital for transfer. This system is inexpensive and has eliminated the need to duplicate specialized equipment for a gamete handling laboratory adjacent to the operating room. New construction charges have been eliminated; and as new egg retrieval methodologies are developed, the use of the mobile laboratory cart will provide our IVF program with maximum flexibility in changing sites within the hospital. Used in conjunction with an extensive quality control program, this modification has not interfered with oocyte fertilizability or with the overall pregnancy rate in the University of Wisconsin IVF program.

Equipment and Supplies, Hospital↗
PubMed1985

A monoclonal antibody to human platelet glycoprotein IIIa detects a related protein in cultured human endothelial cells.

We have previously described a series of monoclonal antibodies against platelet membrane glycoproteins. Two of the antibodies, B59.2 and B2.12, recognize the glycoprotein IIb-IIIa complex. These two antibodies react specifically with glycoprotein (GP) IIIa, as shown by immunoblotting of sodium dodecyl sulfate-polyacrylamide gels of solubilized platelet membranes. Monoclonal B2.12, but not B59.2, binds to cultured human endothelial cells obtained from umbilical vein, internal iliac artery, and inferior vena cava. At saturation approximately 100,000 binding sites were detected per human umbilical vein endothelial cell. When solubilized radioiodinated cells were chromatographed on a column of agarose-bound B2.12, a single radiolabeled protein was obtained whose apparent molecular weight is slightly larger than that of platelet GP IIIa. This protein incorporated [35S]methionine when endothelial cells were labeled metabolically. These results demonstrate that human endothelial cell membranes synthesize a protein immunologically related to platelet GP IIIa.

Antibodies, Monoclonal↗
PubMed1985

Changes in sterol and phospholipid fatty acid composition in Refsum's disease fibroblasts grown in the presence of phytol.

Fibroblasts derived from an individual with Refsum's disease (GM 3896) and a normal control (GM 1717) were grown in the presence of 0, 0.1, 0.2, and 0.3 mM phytol. Cultures were analyzed for total sterol content, and the fatty acid composition of the extractable phospholipids. The fatty acid composition of the phospholipids are similar for control and Refsum's disease fibroblasts when grown on media lacking phytol. However, the addition of phytol to the growth medium produces differences in fatty acid composition between the phospholipids extracted from control and Refsum's disease cells. With regard to sterol composition, data are presented which suggest that an altered sterol is induced in Refsum's disease fibroblasts by the presence of phytol in the growth medium. The possible relationship of these findings to the mechanism of Refsum's disease is discussed.

Cell Line↗
PubMed1984

Artificial donor insemination: fresh versus frozen semen; the patient as her own control.

The efficacies of fresh versus cryopreserved semen in the treatment of male factor infertility by artificial insemination by donor (AID) semen were directly compared by using the patient as her own control. In any one cycle, either fresh or frozen semen was used. The type of semen preparation was randomly assigned for the first cycle and varied thereafter according to donor availability. The same donor was used for a given patient in six consecutive cycles. We treated 381 patients in this way. In 676 cycles fresh semen was used and 128 pregnancies were achieved. Fecundability, the chance of getting pregnant per cycle of exposure, was 18.9% with fresh semen. In 1200 cycles cryopreserved semen was used and 60 pregnancies occurred, for a fecundability of 5.0%. Therefore, in our clinic, fresh semen is more than three times as likely to induce pregnancy as frozen semen. The design that has been used in this therapeutic protocol provides a technique for internal quality control of the cryopreservation process and for the investigation of other variables potentially affecting the success rates with AID.

Female↗
PubMed1984

Kinetic characteristics of beta-carotene uptake and depletion in rat tissue.

Rats were fed a semi-purified diet supplemented with 0, 0.002, 0.02 and 0.2% beta-carotene (BC) for 21 weeks, followed by a 5-week depletion period. At various time points liver, adrenal, ovary, lung, heart, kidney, plasma, skin, brain and muscle were analyzed for BC content. The results indicated a dose-response effect between ingested BC and BC tissue content. The tissue saturation levels of BC, and time to reach saturation were determined in animals fed 0.2% BC diets. The half-life for BC was also determined. There was no apparent relationship among tissue content, rate of uptake and rate of depletion of BC. Each tissue studied was different. The absence of BC in fat suggests to us that BC distribution is not simply a matter of deposition into lipid depots. There was a wide range in tissue levels of BC; liver had the greatest value with 50 micrograms/g tissue, and muscle had the lowest value with 0.03 micrograms/g tissue. Plasma was saturated within 3 days, whereas liver, adrenal and ovary had not yet reached saturation at 147 days. The half-life varied from less than 3 days for plasma to 18 days for muscle.

Adrenal Glands↗