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Biomedical subjects

J McGregor

Publications and source records attributed to J McGregor.

At least 19 recordsLinked to original sources

Human platelet glycoprotein IIIb binds to thrombospondin fragments bearing the C-terminal region, and/or the type I repeats (CSVTCG motif), but not to the N-terminal heparin-binding region.

Major blood membrane platelet glycoprotein IIIb (GPIIIb), also termed GPIV or CD365, has been identified as a receptor for thrombospondin (TSP), collagen and Plasmodium falciparum-infected erythrocytes. The aim of the present study was to identify region(s) of TSP involved in binding of GPIIIb. Proteolytic fragments of TSP (M(r) 140 kDa, 120-18 kDa and 27 kDa on SDS/PAGE under reducing conditions) were purified by f.p.l.c. and identified by N-terminal gas-phase sequencing, e.l.i.s.a. and Western blots using monoclonal antibodies directed against defined domains of TSP. The 140 kDa and 120-18 kDa fragments (C-terminal region), but not the 27 kDa fragment (N-terminal region), were shown to bind to GPIIIb by using e.l.i.s.a. and affinity-chromatography systems. TSP binding to a GPIIIb-affinity column was Ca(2+)-dependent and reduced by 45% in the presence of EDTA. Moreover, TSP was only partially eluted with EDTA from a Ca(2+)-equilibrated GPIIIb column. A fragment of 68 kDa, obtained by further digestion of the 140 kDa fragment, bound to the GPIIIb-Sepharose affinity column. This fragment, or stalk-like region, bears the TSP type I repeats that show sequence similarity to regions on properdin, Plasmodium falciparum proteins and antistasin. Peptides (CSVTCG or SVTCGGGV) representing these repeats bound isolated GPIIIb in a Ca(2+)-independent way, but did not completely inhibit the GPIIIb and TSP interaction. These studies indicate that GPIIIb binds to the TSP via the C-terminal region and/or the CSVTCG motif, but not to the N-terminal region. Interaction between GPIIIb and the TSP C-terminal region or the CSVTCG motif is respectively Ca(2+)-dependent and -independent.

Amino Acid Sequence

Amniotic sheets: natural history and histology.

Eleven amniotic sheets were detected on obstetric ultrasound. Ten of these were reviewed retrospectively and one was followed prospectively throughout gestation. Amniotic sheets are single, planar reflective membranes. Evidence presented here suggests that these membranes are composed of four distinct layers: two layers of chorion sandwiched between two layers of amnion. Their mean thickness is 2.4 mm in the midportion and 4.5 mm at the free edge. A thick triangular base is frequently seen. Amniotic sheets change little during pregnancy; however, they are more difficult to identify late in gestation. They are unassociated with fetal anomalies. Mothers with amniotic sheets had a substantial incidence of previous spontaneous or therapeutic abortions.

Adolescent

Biomechanical assessment of the effects of significant hamstring injury: an isokinetic study.

Soccer players may develop recurrent hamstring injuries. This may be due to inadequate rehabilitation or to recurrent injury. In addition, following injury, the hamstring muscular complex may be permanently damaged, resulting in decreased strength, and increased likelihood of recurrent injury. Fourteen professional soccer players were assessed by clinical examination and by isokinetic testing with a Cybex II machine. Seven had suffered moderate or major hamstring injuries in the past year. There were seven controls. None of the hamstring group were currently suffering from an acute hamstring injury. The results of the two groups were compared. There were no differences in the mean results. This pilot study suggests that no permanent functional damage occurs to the muscular complex after moderate or major hamstring injuries after correct treatment. However, further research is required to confirm this.

Adolescent

Comparative toxicity of cisplatin, carboplatin (CBDCA) and iproplatin (CHIP) in combination with cyclophosphamide in patients with advanced epithelial ovarian cancer.

Sixty patients with FIGO stage IIb, IIc, III and IV ovarian cancer were entered into a randomized Phase III study of cyclophosphamide 600 mg/m2 with cisplatin 100 mg/m2, iproplatin 240 mg/m2 or carboplatin 300 mg/m2. Dose modifications were made according to renal function and myelotoxicity. The arms containing carboplatin (CBDCA) and iproplatin (CHIP) were not shown to be significantly different from the cisplatin containing arm with regard to response rate, duration of response and survival. Subjective toxicity showed that cisplatin and cyclophosphamide therapy was associated with more nausea and vomiting (P = 0.0005). The duration of vomiting showed a significant increase with successive courses of chemotherapy for the cisplatin containing arm only (P less than 0.003). The cyclophosphamide/CHIP combination caused significantly more diarrhoea (P less than 0.0006). Alopecia was more severe (P less than 0.02), and neurotoxicity was more common, in patients who received cyclophosphamide and cisplatin (paraesthesiae P = 0.0007, tinnitus P less than 0.00005, deafness P = 0.0018). All three combinations caused cumulative toxicity on haemoglobin (Hb) (P less than 0.001 for each treatment), leukocyte count (WCC) (P less than 0.0005 for each treatment), and platelet count (P less than 0.0005 for each treatment). The degree of fall in Hb for each course of therapy was greater in the cisplatin containing arm compared with the CHIP and CBDCA arms which were not significantly different from each other (P = 0.0005). For WCC the cisplatin/cyclophosphamide regimen was significantly less toxic than CHIP/cyclophosphamide, with CBDCA/cyclophosphamide falling between the two and not being significantly different from either (P = 0.0005). The CHIP containing arm caused more thrombocytopenia than the other arms which were of equal toxicity (P less than 0.0005). Serum creatinine showed a gradual significant overall rise with each course of cisplatin/cyclophosphamide therapy (P less than 0.0005), whereas the CBDCA arm showed no change and the CHIP arm showed a small fall in serum creatinine after most courses of therapy. This study showed that CHIP or CBDCA in combination with cyclophosphamide was less toxic than cisplatin/cyclophosphamide therapy with regard to alopecia, degree and duration of nausea and vomiting, renal toxicity, neurotoxicity and anaemia. The CHIP/cyclophosphamide regimen caused more thrombocytopenia and diarrhoea. The CHIP and CBDCA containing arms caused more leukopenia than the cisplatin containing regimen. Either iproplatin or carboplatin would be an acceptable alternative to cisplatin in chemotherapy regimens, and would result in reduced toxicity.

Aged

Human chronic myeloid leukemic cell line with positive Philadelphia chromosome exhibits megakaryocytic and erythroid characteristics.

A cell line (LAMA-84) has been established from the blood of a patient with chronic myeloid leukemia in acute phase. LAMA-84 cells retained the patient's chromosome abnormalities, i.e., triplication of all chromosomes except chromosome 18, the presence of Philadelphia (Ph) chromosome in 4-5 copies, and the presence of chromosome markers. LAMA-84 cells have morphological features of undifferentiated blast cells, but analyses have indicated that they belong to the megakaryocytic lineage; platelet peroxidase (PPO) was found in 8.5% of cells; LAMA-84 cells reacted spontaneously with poly- and monoclonal antibodies against the platelet glycoproteins (GP) IIb, IIIa, and the GPIIb/IIIa complex, whose presence was confirmed by crossed immunoelectrophoresis. LAMA-84 cells lack the membrane characteristics of lymphoid and mature granulocytic cells but do, however, react with certain antibodies to immature myeloid cells. Furthermore, they are positive with an antiglycophorin antibody, and contain alpha- and gamma-globin mRNA, thus demonstrating erythroid marker expression. Thus LAMA-84 is a tripotent, megakaryocytic, erythroid, and granulocytic cell line. The megakaryocytic and erythroid markers were enhanced by the addition of DMSO, butyrate, TPA, and hemin. The LAMA-84 cell line represents an interesting tool for the study of megakaryocytic and erythroid differentiation and the mechanisms of neoplastic growth.

Adult

Perinatal pertussis.

Pertussis (whooping cough), a highly contagious disease of childhood, is increasingly recognized among reproductive-age adults and neonates. Described are three cases of maternal-infant pairs in which mother-to-newborn transmission probably occurred and was the cause of extensive morbidity and cost. Means of recognition, treatment, handling, and prevention of this potentially lethal childhood illness are discussed.

Erythromycin

Plasma thrombospondin in patients with chronic renal failure, liver disease and splenectomy.

Thrombospondin (TSP), is a major constituent of human blood platelet alpha-granules. Stimulation of platelets causes the release of TSP in parallel with other alpha-granule constituents such as beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) but the thrombospondin plasma in vivo half life is significantly greater than beta-TG and PF4. The aim of this study was to assay TSP levels in plasma of patients with chronic renal failure (CRF), liver disease (LD) and following splenectomy. The TSP values were then compared to the patients plasma levels of two traditional markers of platelet activation, beta-TG and PF4, and to fibronectin (FN) and von Willebrand factor (VIII:vWF). Plasma TSP levels (67.6 +/- 16.9 ng/ml) assayed in 14 CRF patients were significantly higher (p less than 0.05) than those measured in 28 donors (55.5 +/- 11.7 ng/ml). No correlation was observed, in CRF patients, between the TSP level and PF4 (2.5 +/- 1.5 ng/ml), beta-TG (131.1 +/- 21 ng/ml), FVIII:vWF (252 +/- 85%), or FN (102 +/- 33%) plasma levels. The TSP plasma level in CRF patients was significantly correlated (p less than 0.02) with that of fibrinopeptide A (4.1 +/- 1.9 ng/ml). Although the beta-TG (23.5 +/- 6.9 ng/ml) and PF4 (2.9 +/- 2 ng/ml) plasma levels in six LD patients were normal, the TSP levels (82.5 +/- 39.1 ng/ml) were significantly increased (p less than 0.01). Thrombospondin plasma levels (77.1 +/- 20.1 ng/ml) in 14 patients having undergone splenectomy were significantly increased (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Prediction of recurrence after mastectomy for operable breast cancer.

A patient's risk of early recurrence after mastectomy for breast cancer has been estimated by using a combination of four prognostic factors. A computer program, designed to calculate the exact probability of recurrence within 2 years of mastectomy, was accurate when tested on 240 patients. A simple scoring system could identify patients at lower and greater risk than any single factor alone.

Breast Neoplasms

An epidemic of "childbed fever".

Postpartum infection remains a cause of considerable maternal morbidity and occasional maternal mortality. Puerperal sepsis mediated by what is now known as group A beta-hemolytic streptococci or Streptococcus pyogenes was once a common and lethal nosocomial scourge. Fortunately, multiple developments have decreased the incidence and ameliorated the clinical course of group A beta-hemolytic streptococcal postpartum sepsis. Despite these developments, epidemic group A streptococcal sepsis still jeopardizes modern mothers. We describe an epidemic of five women with group A beta-hemolytic streptococci-mediated postpartum infections which occurred at Mather Air Force Base Hospital, Sacramento, California. The remarkable, yet characteristic signs, symptoms, and clinical course of these patients are briefly reviewed along with the epidemiologic methods which led to the discovery of the common nosocomial source. Familiarization of the clinical aspects of these patients and the methods used to eradicate this epidemic will facilitate the protection and care of other women. Unfortunately, modern mothers still remain in jeopardy from "childbed fever."

California

A radioimmunoassay for thrombospondin, used in a comparative study of thrombospondin, beta-thromboglobulin and platelet factor 4 in healthy volunteers.

A radioimmunoassay was developed for the platelet alpha-granule protein thrombospondin; concentrations of thrombospondin as low as 3 ng ml-1 could be measured. There was no interference from other components of human biological fluids and no crossreactivity with beta-thromboglobulin (beta-TG) or platelet factor 4 (PF4). Plasma samples were stable when stored at -20 degrees C. Normal human plasma contained 105.0 +/- 31.0 ng thrombospondin ml-1 compared with beta-TG concentrations of 37.2 +/- 10.9 ng ml-1 and PF4 concentrations of 14.7 +/- 10.1 ng ml-1 when samples were carefully taken into a platelet inhibitor cocktail and processed at 0-4 degrees C. Release of thrombospondin during clotting of blood occurred at the same time as that of beta-TG and PF4 and resulted in a serum concentration of 17.5 +/- 5.5 micrograms ml-1. Assay of whole blood gave a platelet thrombospondin content of 89.1 +/- 28.3 ng/10(6) platelets. The concentration in normal urine fluctuated widely from 3 to 22.5 ng ml-1, and was unrelated to urine flow. The half-life of thrombospondin in vivo was about 9 h, much longer than that of either beta-TG or PF4. Unlike PF4, it was not released into the blood following an intravenous heparin injection. Bovine, ovine, canine and porcine sera contained thrombospondin which crossreacted immunologically with the human molecule; these species would be suitable animal models for the study of thrombospondin and its value as a platelet release marker.

Adult

Solubilization of an alpha-bungarotoxin-binding component from rat brain.

Binding of [125I]-alpha-bungarotoxin to rat brain was investigated. Picomole quantities of specific toxin binding sites per gram of fresh tissue were found in particulate preparations as well as detergent extracts of whole brain. The toxin-binding macromolecules can be solubilized in low concentrations of Triton X-100. Specific binding occurs to a single class of sites with a dissociation constant of 5.6 X 10(-11) M. The association rate constant in 10 mM sodium phosphate, pH 7.4, was determined to be 6.8 X 10(5) M-1 s-1; the half-life of the complex was found to be 5.1 h, corresponding to a dissociation rate constant of 3.8 X 10(-5) s-1. The binding macromolecules resemble peripheral nicotinic acetylcholine receptors in toxin binding kinetics, solubility, isoelectric point, and hydrodynamic properties.

Animals

The evolutionary development of modifier genes.

The main findings of a study of the evolution of modifier gene frequencies in models of deterministic population genetics are presented. A wide variety of random mating systems are subject to selection with modifiers operating, in different cases, on mutation rates, dominance, migration between subpopulations, and linkage between other loci. In all these instances the modifier frequencies evolve in such a way as to maximize the mean fitness of the population at equilibrium. This is remarkable since, except for the dominance modifier, the modifier genes are selectively neutral in the sense that they do not affect the fitness of their individual carriers. In nonrandom mating systems the mean fitness concept is not well defined, and there does not appear to be such a simple principle governing the evolution of modifier frequencies. In assortative mating systems modifiers favoring reduced assortment propensities tend to increase. In contrast, for selfing-outcrossing systems modifiers favoring increased selfing tend to increase.

Alleles