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Biomedical subjects

J McGregor

Publications and source records attributed to J McGregor.

At least 19 recordsLinked to original sources

Drawbacks of the MAIPA technique in characterising human antiplatelet antibodies.

Monoclonal Antibody-specific Immobilisation of Platelet Antigens (MAIPA) assays have been developed to allow the identification and characterisation of antibodies directed against platelets. A major disadvantage of the MAIPA test is the existence of false negative results. This is due to the competition between human and monoclonal antibodies (MoAb) for epitopes that are either identical or very close. In this report we used the MAIPA technique to test anti-HPA-1a alloantibodies and anti-Naka isoantibodies in conjunction with a panel of murine MoAbs directed against CD41/61 or CD36 respectively. Our data demonstrate that the choice of MoAbs used in MAIPA is very important for accurate diagnosis of clinical conditions and institution of specific therapy. Moreover, the results obtained are in favour of an heterogeneity for the recognition of the alloepitope HPA-1a and of distinguishable epitopes on GPIV.

Antibodies, Monoclonal

Outbreak of HIV infection in a Scottish prison.

OBJECTIVE--To investigate the possible spread of HIV infection and its route of transmission among prison inmates. DESIGN--In response to an outbreak of acute clinical hepatitis B and two seroconversions to HIV infection, counselling and testing for HIV were offered to all inmates over a two week period in July 1993. Information was sought about drug injecting, sexual behaviour, and previous HIV testing. SETTING--HM Prison Glenochil in Scotland. SUBJECTS--Adult male prisoners. MAIN OUTCOME MEASURES--Uptake of HIV counselling and testing; occurrence and mode of HIV transmission within the prison. RESULTS--Of a total 378 inmates, 227 (60%) were counselled and 162 (43%) tested for HIV. Twelve (7%) of those tested were positive for antibody to HIV. One third (76) of those counselled had injected drugs at some time, of whom 33 (43%) had injected in Glenochil; all 12 seropositive men belonged to this latter group. Thirty two of these 33 had shared needles and syringes in the prison. A further two inmates who injected in the prison were diagnosed as positive for HIV two months previously. Evidence based on sequential results and time of entry into prison indicated that eight transmissions definitely occurred within prison in the first half of 1993. CONCLUSION--This is the first report of an outbreak of HIV infection occurring within a prison. Restricted access to injecting equipment resulted in random sharing and placed injectors at high risk of becoming infected with HIV. Measures to prevent further spread of infection among prison injectors are urgently required.

Adult

Elevated protease activities in human amnion and chorion correlate with preterm premature rupture of membranes.

OBJECTIVES: The mechanism(s) of preterm premature rupture of fetal membranes resulting in preterm birth remains unknown. Studies suggest that fetal membranes are susceptible to weakening by protease attack and that collagenases may be active at the site of rupture. In this study fetal membranes from women delivered after preterm premature rupture of membranes were compared with control membranes and analyzed qualitatively and quantitatively for protease activities. STUDY DESIGN: Fourteen membranes from women with preterm premature rupture of membranes and nine membranes from women delivered preterm without premature rupture of membranes or otherwise normal women delivered at term vaginally or by cesarean section were studied. Zymogram gel electrophoresis with gelatin incorporation was used to assess the number and apparent molecular weights of protease activities. Functional and quantitative studies of protease activity were measured by fluorescent substrate cleavage. RESULTS: Zymogram gel electrophoresis studies demonstrated the presence of five to seven different protease bands in preterm premature rupture of membranes samples, whereas control membranes demonstrated only one to three protease bands. Fluorescent studies of protease activity demonstrated a 10- to 40-fold increase in activity in membranes from women with preterm premature rupture of membranes compared with normal control membranes. Studies with protease inhibitors suggest that most of the activity is due to metalloproteinases. CONCLUSION: In membranes from women with preterm premature rupture of membranes there appears to be a general increase in the amount of protease activity and increased numbers of putatively different proteases. Increased activity or deregulated protease control may mediate preterm premature rupture of membranes and be a potentially remediable cause of preterm birth.

Amnion

Thrombospondin in human glomerulopathies. A marker of inflammation and early fibrosis.

Extensive damage is thought to occur to endothelial cells in renal vasculitis and other glomerulopathies. The state of inflammation of these endothelial cells was investigated through the use of a panel of monoclonal antibodies (MAb) directed against thrombospondin (TSP), von Willebrand factor (vWF), integrins (alpha IIb beta 3, alpha v beta 3), CD36, and classical markers of inflammation (P-selectin, E-selectin, ICAM-1, VCAM). Results show that the anti-TSP MAb (LYP10) stains large areas of interstitium in focal sclerosis, vasculitis, membranous glomerulonephritis (GN), and diabetic GN but does not in normal kidney. In contrast, very limited areas are stained by LYP10 in minimal change nephropathy and Berger's disease. On paraffin-embedded specimens these areas stained by LYP10 appear edematous and early fibrous. Up-regulation of vWF and ICAM-1 is matched by an increased binding of LYP10 to the interstitium. In addition, fibrous crescents in injured glomeruli are stained by LYP10. This study reports for the first time an increased TSP secretion in glomerulopathies. Such TSP secretion may be part of physiological adaptive changes associated with inflammation and early fibrosis.

Antibodies, Monoclonal

Spontaneous fracture of the outlet catheter of a totally implanted catheter system (Port-A-Cath).

A case of spontaneous fracture of the outlet catheter of a totally implanted catheter system (Port-A-Cath) is presented. The outlet catheter was fractured at the entrance into the left subclavian vein twenty-one weeks after insertion and the distal part was embolized in the right ventricle. The embolized catheter fragment was retrieved by a 'goose-neck' snare via the right femoral vein. The awareness of a possible spontaneous fracture of the outlet catheter of a totally implanted catheter system (Port-A-Cath) is important to prevent accidental spillage of potent cytotoxic substances.

Adolescent

A P-selectin/CD62P monoclonal antibody (LYP-20), in tandem with flow cytometry, detects in vivo activated circulating rat platelets in severe vascular trauma.

P-selectin, also known as CD62P, GMP140 or PADGEM, is present in platelet alpha-granules and endothelial cell Weibel-Palade bodies and is very rapidly expressed on the surface of these cells on activation. In this study, an anti P-selectin monoclonal antibody (LYP20) was used, in tandem with flow cytometry, to identify activated platelets at the site of induced vascular trauma or in peripheral blood. Moreover, electron microscopy was performed to characterize sites of vascular trauma and quantify the number of adhering platelets. The same induced vascular trauma was observed to result into animals responding in 2 different ways (Group I, Group II) following the degree of platelet activation. Five rats, out of 14 with induced vascular trauma, had more than half of their circulating platelets expressing P-selectin when drawn at the site of the trauma (67.4% +/- 3.44) or in peripheral blood (78.5% +/- 2.5) (Group I). In the remaining 9 animals a much smaller proportion of circulating platelets expressed P-selectin when assayed from trauma sites (18% +/- 3.34) or in peripheral blood (18.0% +/- 4.30) (Group II). Enhanced P-selectin expression by circulating platelets in Group I, compared to Group II, appears to be linked to the degree of activated platelets adhering at sites of trauma (171 +/- 15 x 10(3) platelets versus 48 +/- 31 x 10(3) platelets per mm2). In the 5 control animals, that were not operated on, platelets expressing P-selectin when drawn at the site of a mock trauma (7.0% +/- 1.84) or in the peripheral blood (11.2% +/- 3.30) showed little activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Detection of Trichomonas vaginalis in pregnant women with the InPouch TV culture system.

Trichomonas vaginalis causes a common genitourinary infection which is frequently asymptomatic. At present, pregnant women are not usually screened for the infection unless they are symptomatic. In the present study, we screened and obtained samples for culture from all pregnant women attending a prenatal clinic with the InPouch TV culture system and compared results with those of standard culture in Diamond's medium and slide wet mount examination. The InPouch TV culture system was as reliable as Diamond's medium in detecting T. vaginalis and may be useful and effective in a pregnancy clinic setting.

Animals

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