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Biomedical subjects

R B Harris

Publications and source records attributed to R B Harris.

At least 163 records · Page 9Linked to original sources
PubMed1981

Partial purification of biologically active, low molecular weight, human antihemophilic factor free of Von Willebrand factor. II. Further purification with thiol-disulfide interchange chromatography and additional evidence for disulfide bonds susceptible to limited reduction.

Thiol-disulfide interchange chromatography was used in the preparation of partially purified (approx. 17 000-fold) low molecular weight, Mr approximately or equal to 115 000, human antihemophilic factor essentially free of Von Willebrand factor. This antihemophilic factor was prepared from fresh plasma which had undergone limited reduction with 1 mM dithiothreitol and was subsequently reacted with 2,2'-dipyridyl disulfide, a sulfhydryl reagent which readily undergoes disulfide exchange. Exchange of protein-2-pyridyl mixed disulfide with thiopropyl-Sepharose resulted in the chromatographic adsorption of approx. 96% of the coagulant activity, of which approx. 20% subsequently eluted with 1.0 mM dithiothreitol. After reductive displacement from the thiopropyl-Sepharose the antihemophilic factor could be S-alkylated with iodo-[1-14]acetamide. The ratio of coagulant activity to Von Willebrand factor-antigen activity was greater than 30 000 : 1. In contrast, reduced antihemophilic factor was alkylated with iodoacetamide prior to chromatography as a control, and showed no exchange with the thiopropyl-Sepharose, eluting quantitatively in the breakthrough volume. These studies reinforce our previous results (Harris, R.B., Newman, J. and Johnson, A.J. (1981) Biochim. Biophys. Acta 668, 456-470) that partial reduction with dithiothreitol exposes critical sulfhydryl groups which, when alkylated, maintains the antihemophilic factor in a low molecular weight form without inactivating procoagulant activity.

Chromatography↗
PubMed1979

Freedom from transmission of hepatitis-B of gamma-globulin and heat-inactivated plasma protein fraction prepared from contaminated human plasma by fractionation with solid-phase polyelectrolytes.

Plasma contaminated with hepatitis B surface antigen (HBsAg) and shown by others to be infectious when injected in a dilution of 1:1,000,000 in chimpanzees, was fractionated by a solid-phase polyelectrolyte (PE) procedure for its content of plasma protein fraction (PPF) and gamma-globulin (immune serum globulin; ISG). Quantitative Ausria II radioimmunoassays showed that nearly half the HBsAg was bound by the PE and could be eluted at low pH, while the rest was found in the heat-inactivated PPF. When the ISG was concentrated to 16%, the 13 mg/kg (comparable to a human dose) was injected intramuscularly in 6 chimpanzees, or when the PPF was heated at 60 degrees C for h and injected intravenously in 2 chimpanzees, there was no clinical or laboratory evidence of hepatitis B infection after 12 months, although 1 chimp of 2 who received the same material showed a borderline positive anti-HBsAg antibody result on one of 52 weekly serum samples. Since the new PE fractionation method is essentially nondenaturing, and simpler than the classical ethanol procedures, it was important to establish the noninfectivity of the final products.

Adsorption↗
PubMed1979

Lichenoid delayed hypersensitivity reactions in tattoos.

Two patients with an inflammatory reaction in a red tattoo had histopathologic changes of lichen planus. The lesions demonstrated a lymphocytic bandlike infiltrate, liquefaction degeneration, acanthosis, hypergranulosis, and orthokeratosis and many hyaline bodies. Metal particles were observed in the region of the dermal-epidermal reaction. This probably is another example of the lichenoid reaction produced by delayed cellular hypersensitivity.

Adult↗
PubMed1979

Treatment of scleromyxedema with melphalan.

Scleromyxedema is an uncommon cutaneous fibromucinous disease with a monoclonal protein, which has resisted a number of therapies. Eight cases followed up for as long as 12 years have provided an opportunity to observe the effects of melphalan treatment in this disease. The fibrohistiocytic and mucinous change of the skin in scleromyxedema and often the monoclonal protein can be controlled by low-dose chemotherapy. Although melphalan does not usually produce clinical toxic effects of importance, it is a myelotoxic drug and cytopenia is common; one patient died of acute myelomonocytic leukemia after ten years of successful therapy of the scleromyxedema, thus implying that long-term therapy may be dangerous by itself. These patients require close supervision. Leukocyte and platelet counts must be performed every three weeks, and the dosage of melphalan adjusted accordingly.

Adult↗
PubMed1979

Lymphoid follicles in subcutaneous inflammatory disease.

A review of inflammatory subcutaneous disease revealed that lymphoid follicles are observed frequently in lupus panniculitis. They are found rarely in other lymphocytic inflammatory diseases involving the panniculus, such as morphea, erythema nodosum, and erythema induratum. The lymphoid follicle may be an indication of immunoreactive and connective tissue disease, and cases should be evaluated with this in mind.

Adipose Tissue↗
PubMed1978

Generalized elastolysis (cutis laxa).

Generalized elastolysis is a rare and unique systemic disorder of connective tissue in which the elastic fibers suddenly become fragmented, disorganized and fewer in number with the resultant production of such entities as cutis laxa, emphysema, aortic aneurysms and bowel diverticula appearing in the organ system involved, that is, skin, lung, vasculature or gastrointestinal tract. Presented here are three cases that, illustrate the typical features of this condition. In addition, 14 more cases were retrieved from the literature and the information reviewed. Various etiologic factors relating to the synthesis and degradation of elastic tissue are discussed in light of recent findings in the biochemistry of connective tissue.

Adult↗
PubMed1978

Cytoplasmic estrogen receptors and estrogen concentrations in bovine uterine endometrium.

Specific cytoplasmic binding of 17beta-[3H]estradiol ([3H]E2beta) by unoccupied receptors in bovine uterine endometrium was determined by saturation analysis and correlated with endometrium levels of E2beta in 21 cows. The concentrations of these estrogen receptors (ER) during the estrous cycle were significantly greater during proestrus, estrus, and postestrus (days 18-20 and 0-4 of the cycle) than during the midluteal period (days 10-12; P less than 0.05). These increases in ER concentration paralleled increases in endometrial and plasma E2beta concentrations. In a preliminary experiment involving six heifers killed during the estrous cycle, a comparison of the ER concentrations of the horns ipsilateral and contralateral to the corpus luteum showed no significant differences, as did a study of the dissociation constant of the steroid-receptor interaction during the estrous cycle and early pregnancy. The order of inhibition of cytoplasmic binding of [3H]E2beta by estrogens was as follows: E2beta greater than E1 greater than E2alpha greater than E3 at 4 C. The concentration of ER in six pregnant animals was higher on days 2-3 than on days 13-14 after insemination, which was similar to that found in cycling animals; however, the difference between days was not significant. Ovariectomy of two heifers resulted in slightly higher ER concentrations than in intact heifers, whereas immunization of two heifers with an E2beta conjugate resulted in levels 2-fold higher. In these altered animals plasma progesterone (P4) was nearly nondetectable. ER concentration was inversely related to the level of plasma P4 in cycling heifers (r = -0.58, P less than 0.01). Endometrial estrogen and plasma estrogen levels were also inversely correlated with plasma P4 levels (r = -0.65, P less than 0.01 and r = -0.48, P less than 0.05, respectively). Thus, if P4 level influences ER levels, the hormone may make the tissue less responsive to ovarian estrogens at such time as the luteal phase of the cycle and during pregnancy.

Animals↗
PubMed1978

Lupus mastitis.

Two patients with long-standing discoid lupus erythematosus developed tender, discrete breast nodules that, on the mammogram, were interpreted as carcinomas. The histologic features, direct immunofluorescence findings, and laboratory data confirmed the diagnosis of lupus mastitis. Antimalarial therapy resulted in the complete resolution of the lesions.

Adult↗
PubMed1977

Detection of hepatitis B surface antigen in potentially contaminated human plasma and plasma fractions.

A new method is described for the quantitative detection of HBsAg in whole human plasma and in plasma fractions. The nonantigen proteins are digested with pepsin at low pH, and the antigen is precipitated with PEG. With use of only 20 ml of contaminated plasma, as few as 5.0 x 10(6) HBsAg particles/ml can be detected--a 40-fold increase in the apparent level of sensitivity of the Ausria II RIA (2.0 x 10(8) particles/ml). With 500 500 ml or more of plasma or plasma fractions, fewer than 5.0 x 10(5) particles/ml can be assayed--a 400-fold increase in RIA sensitivity and 1/10 the antigen concentration found in sera that proved infective when injected into chimpanzees. The pepsin-PEG method was used to quantitate the particles per milliliter in four equivocal RIA samples from the NIH Bureau of Biologics, three of which were definitely shown to contain antigen. The method has also been employed to detect fewer than 2.0 x 1010(8) particles/ml of HBsAg in deliberately contaminated high purity AHF concentrates and may be useful for monitoring plasma fractions prepared on a large scale or for detecting the antigen in equivocal samples from blood banks.

Blood Donors↗
PubMed1976

Removal of hepatitis B surface antigen (HBsAg) from plasma fractions.

Endogenous or deliberately added hepatitis B antigen was removed and concentrated for assay from albumin, and from coagulation factor II, VII, IX, and X concentrates as model plasma fractions. The concentrates carry considerable risk of causing hepatitis in transfused patients. The amount of antigen remaining in the fraction was estimated to be less than 1/10,000 of that detectable by the Ausria II radioimmunoassay and 1/100 of that found to be infectious when highly contaminated human sera were diluted and injected in chimpanzees. Batch fractionation methods with polyethylene glycol were used. The yield of albumin was 96 per cent and of the coagulation factors about 90 per cent.

Blood Proteins↗