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Biomedical subjects

A Jackson

Publications and source records attributed to A Jackson.

At least 307 records · Page 17Linked to original sources

Recovery of mitogenic activity of a growth factor mutant with a nuclear translocation sequence.

Heparin-binding growth factor-1 (HBGF-1) is an angiogenic polypeptide mitogen for mesoderm- and neuroectoderm-derived cells in vitro and remains biologically active after truncation of the amino-terminal domain (HBGF-1 alpha) of the HBGF-1 beta precursor. Polymerase chain reaction mutagenesis and prokaryotic expression systems were used to prepare a mutant of HBGF-1 alpha lacking a putative nuclear translocation sequence (amino acid residues 21 to 27; HBGF-1U). Although HBGF-1U retains its ability to bind to heparin, HBGF-1U fails to induce DNA synthesis and cell proliferation at concentrations sufficient to induce intracellular receptor-mediated tyrosine phosphorylation and c-fos expression. Attachment of the nuclear translocation sequence from yeast histone 2B at the amino terminus of HBGF-1U yields a chimeric polypeptide (HBGF-1U2) with mitogenic activity in vitro and indicates that nuclear translocation is important for this biological response.

Amino Acid Sequence↗

Usefulness of a systemic hypertension in-hospital educational program.

The effects of an educational program on compliance and blood pressure (BP) control were assessed in 47 hypertensive patients hospitalized for nonhypertension-related diseases. Patients were randomized to receive either a questionnaire and an educational program (group I, 25) or questionnaire only (group II, 22). Baseline clinical characteristics, admission diagnoses and antihypertensive medications were similar between the groups. Antihypertensive medications used by patients before the trial were not changed. Eight weeks after the initial intervention, patients in group I showed a significant reduction in both systolic and diastolic BP (137/89 vs 154/98 mm Hg, p = 0.005 and 0.006, respectively) and improved compliance (96 vs 36%, p = 0.04), compared with patients in group II. An education program in patients with high BP is an effective method to improve compliance and BP control in the short-term.

Aged↗

Double-blind placebo controlled study of vancomycin prophylaxis for central venous catheter insertion in cancer patients.

To assess whether vancomycin administration at the time of central venous catheter insertion would prevent catheter-related sepsis (CRS) in immunocompromised patients, 98 cancer patients were entered into a randomized placebo-controlled trial. Patients were stratified according to whether they were having therapy for acute leukaemia or undergoing bone-marrow transplantation (group A) or required chemotherapy for a solid tumour (group B). Eligible patients were randomized to receive either 500 mg vancomycin in 250 ml of 0.9% saline prior to catheter insertion followed by a further 500 mg infused via the established catheter, or the same regimen with 0.9% saline alone. In group A, there were 32 instances of CRS occurring in 20 of the 35 evaluable catheters (57%). Six catheters were removed because of CRS. No significant difference was found in the incidence of CRS between the two arms. Of the 37 evaluable catheters in group B, CRS occurred in 6 (16%), and none of the catheters required removal because of CRS. Again, no significant differences were found in the incidence of CRS between the patients given vancomycin or placebo. These findings indicate that the incidence of CRS is greater in patients who have more severe and prolonged immunosuppression and that vancomycin prophylaxis fails to reduce CRS in patients undergoing chemotherapy for malignant disease.

Adolescent↗

Prognostic significance of osteopenia and immunoparesis at presentation in patients with solitary myeloma of bone.

In a prospective study of 32 patients with solitary myeloma of bone treated between 1974 and 1984, the median survival was 117 months. Twenty of the patients developed multiple myeloma with a median time to dissemination of 46 months. A multivariate analysis of presenting prognostic factors identified osteopenia (P less than 0.000003) and immunoparesis (P less than 0.00002) as the only independent prognosticators of overall survival. The removal of patients with osteopenia or immunoparesis at presentation identified a group of patients with 80-90% chance of surviving 10 years. Patients with either of the risk factors have a median survival of 27 months similar to patients with multiple myeloma, and should be considered for early systemic treatment.

Adult↗

An analysis of the validity of the three-mile run as a field test of aerobic capacity in college males.

The purpose of the present investigation was to examine the concurrent and construct validity of the three-mile (4.83 km) run as a field test of aerobic capacity. Subjects included 109 college-aged males whose three-mile run time (M = 1310.31 +/- 184.48 s) was measured. Fifty of the subjects were given a maximal treadmill stress test, and their peak oxygen consumption (VO2peak) (M = 54.23 +/- 7.08 ml.kg-1.min-1) was measured. The three-mile run was conducted on an outdoor 0.25 mile (0.425 km) track, and split times were recorded each 110 yds (100.32 m) for the first and last laps and total time was recorded for laps 2 through 11. The correlation coefficient between the run time and VO2peak was -.58, indicating only moderate concurrent validity for the run as a field test for aerobic capacity. A factor analysis conducted on the split time data revealed a three-factor structure of a stable pace phase, an initial sprint, and a final sprint with the stable pace factor accounting for most of the common factor variance (69%). The three-mile run time was used to discriminate successfully between two known groups of subjects in aerobic capacity. These data provide a degree of support for the construct validity of the three-mile run as a field test of aerobic capacity.

Adult↗

Detection of high levels of heparin binding growth factor-1 (acidic fibroblast growth factor) in inflammatory arthritic joints.

The synovium from patients with rheumatoid arthritis (RA) and LEW/N rats with streptococcal cell wall (SCW) arthritis, an experimental model resembling RA, is characterized by massive proliferation of synovial connective tissues and invasive destruction of periarticular bone and cartilage. Since heparin binding growth factor (HBGF)-1, the precursor of acidic fibroblast growth factor (FGF), is a potent angiogenic polypeptide and mitogen for mesenchymal cells, we sought evidence that it was involved in the synovial pathology of RA and SCW arthritis. HBGF-1 mRNA was detected in RA synovium using the polymerase chain reaction technique, and its product was immunolocalized intracellularly in both RA and osteoarthritis (OA) synovium. HBGF-1 staining was more extensive and intense in synovium of RA patients than OA and correlated with the extent and intensity of synovial mononuclear cell infiltration. HBGF-1 staining also correlated with c-Fos protein staining. In SCW arthritis, HBGF-1 immunostaining was noted in bone marrow, bone, cartilage, synovium, ligamentous and tendinous structures, as well as various dermal structures and developed early in both T-cell competent and incompetent rats. Persistent high level immunostaining of HBGF-1 was only noted in T-cell competent rats like the disease process in general. These observations implicate HBGF-1 in a multitude of biological functions in inflammatory joint diseases.

Animals↗

A phase I-II study evaluating the murine anti-IL-2 receptor antibody 2A3 for treatment of acute graft-versus-host disease.

A murine IgG1 antibody specific for the IL-2-binding site on the human lymphocyte IL-2 receptor beta chain (CD25) was evaluated in 11 patients who developed acute graft-versus-host disease following allogeneic marrow transplantation. All patients had received cyclosporine and methotrexate for prophylaxis of GVHD, either alone (4 cases), or in combination with antithymocyte globulin (4 cases) or with prednisone (3 cases). Patients had developed GVHD at 7-53 days (median 12) after transplantation and had failed treatment with corticosteroids for 3-44 days (median 19). Residual GVHD was of grade II severity in 4 patients, grade III in 5 patients, and grade IV in 2 patients. Sequential patients received monoclonal antibody in escalating doses from 0.1 mg/kg/day to 1.0 mg/kg/day for 7 days. Side effects were fever, respiratory distress, hypertension, hypotension, and chills occurring in 11 of 72 (14%) antibody infusions. Trough antibody levels greater than 6 micrograms/ml were achieved in patients treated with 0.5 or 1.0 mg/kg/day. Four of eight evaluable patients had an IgM antibody response, and one had an IgG response to the murine immunoglobulin. Clinical response of GVHD was evaluated in 10 patients who received the entire course of the antibody treatment. Among 7 patients treated within 40 days from transplantation, one patient had a complete response in the skin as the only involved organ, and 3 patients had a partial response, 2 in the skin and one in the gastrointestinal tract. No responses were achieved with liver disease at anytime or in any organ in patients treated beyond 40 days after transplantation. Since administration of this antibody was well tolerated and some efficacy was observed in patients with acute GVHD treated early after transplantation, there is a rationale for testing this antibody as an agent for prophylaxis of GVHD.

Acute Disease↗

A case of POEMS syndrome associated with essential thrombocythaemia and dermal mastocytosis.

We describe a case of POEMS syndrome presenting with the recognized features of polyneuropathy, organomegaly, endocrine abnormalities, monoclonal protein, skin changes and anasarca. The patient was found to have both a solitary sclerotic plasmacytoma of the pelvis and evidence of Castleman's disease of lymph nodes. A number of unusual and unique features are also documented. Histological examination of affected skin demonstrated changes similar to urticaria pigmentosa including local oedema and mast cell infiltration. There was marked thrombocythaemia which has been seen in only one previous case and in addition the patient developed diffuse vascular calcification in the absence of recognized aetiological factors. Radiotherapy of the pelvic lesion and chemotherapy to control the myeloproliferative disorder gave rise to significant improvement in neuropathy. Control of anasarca required steroid therapy in addition to diuretics. The significance of these observations is discussed in relation to previous reports.

Adult↗

The borderline diagnosis in adolescents: symptoms and developmental history.

Adult criteria for borderline personality disorder distinguished a group of 27 inpatient adolescent girls from 23 nonborderline inpatient female comparison subjects. The two groups were compared on retrospectively assessed variables measuring psychological, familial, and constitutional factors. Variables most likely to predict borderline personality disorder included history of disrupted attachments, maternal neglect, maternal rejection, grossly inappropriate parental behavior, number of mother and father surrogates, physical abuse, and sexual abuse. Families of borderline adolescents were chronically disrupted, particularly during the patients' early childhoods. The traumatic childhood experiences of the borderline adolescents were similar to those of adults with borderline personality disorder in recent studies.

Adolescent↗

Genucom knee analysis system: reproducibility and database development.

The Genucom is a relatively new computerized system that performs a multidimensional analysis of knee laxity. Therefore, the purposes of the present investigation were twofold: 1) to estimate the reproducibility of the testing system in its ability to obtain similar test values on the same test subject within a back-to-back two-test protocol and 2) to develop a database of normal values as a standard against which values of suspected ligament injury can be compared to reliably determine whether, in fact, ligament injury has occurred. In the reproducibility phase of the study, 20 subjects were tested in two trials each of eight tests, yielding 20 separate test values per trial, accounting for each angle of flexion and plane of force tested. Both legs were tested, providing an N of 40. Test-retest correlations of the two trials and dependent t-tests indicated that the Genucom provided generally stable and reproducible results. In the normal value database phase of the study, 218 different subjects were given one trial of the same eight tests. Testing of both legs provided an N greater than 400. Means and standard deviations were calculated for each test.

Adult↗

Oxytocin infusion during second stage of labour in primiparous women using epidural analgesia: a randomised double blind placebo controlled trial.

OBJECTIVE: To determine whether the high rate of forceps delivery associated with the use of epidural analgesia could be reduced through giving an intravenous infusion of oxytocin during the second stage of labour. DESIGN: A randomised, double blind, placebo controlled trial. SETTING: Delivery suites in three hospitals. SUBJECTS: 226 Primiparous women with adequate epidural analgesia in whom full dilatation of the cervix had been achieved without prior stimulation with oxytocin. INTERVENTION: An infusion of oxytocin or placebo starting at the diagnosis of full cervical dilatation at an initial dose rate of 2 mU/min increasing to a maximum of 16 mU/min. MAIN OUTCOME MEASURES: The outcome of labour was assessed in terms of the duration of the second stage, mode of delivery, fetal condition at birth, postpartum blood loss, and the incidence of perineal trauma. RESULTS: Treatment with oxytocin was associated with a shorter second stage (p = 0.01), a reduction in the number of non-rotational forceps deliveries (p = 0.03), and less perineal trauma (p = 0.03) but was not associated with any reduction in the number of rotational forceps deliveries performed for malposition of the occiput. No adverse effects on fetal condition at birth or in the early puerperium were seen in association with the use of oxytocin. CONCLUSIONS: The use of an oxytocin infusion may reduce the high rate of operative delivery associated with epidural analgesia provided that the fetal occiput is in an anterior position at the onset of the second stage of labour but within the dose range studied does not seem to correct malposition of the fetal occiput.

Adolescent↗

Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis.

The effect of tumour necrosis factor (TNF alpha) antibodies on synovial cell interleukin-1 (IL-1) production was investigated in 7 patients with rheumatoid arthritis and in 7 with osteoarthritis. Synovial cell IL-1 production was significantly reduced by anti-TNF alpha antibody in cultures from patients with rheumatoid arthritis, but antilymphotoxin antibody did not have this effect (except in 1 culture). In cultures from patients with osteoarthritis spontaneous IL-1 production was low, despite high concentrations of TNF alpha, and IL-1 production was not inhibited by anti-TNF alpha antibody. In rheumatoid arthritis, TNF alpha may be the main inducer of IL-1, and anti-TNF alpha agents may be useful in treatment.

Adult↗

Conditioned taste aversions induced by phencyclidine and other antagonists of N-methyl-D-aspartate.

Taste aversions can be conditioned in rats by a variety of psychoactive drugs, including those with reinforcing properties. Previous research, however, has not established clearly whether phencyclidine and related drugs are active in such procedures. The present study was carried out to investigate whether phencyclidine would induce a conditioned taste aversion and whether several other compounds (MK-801, the stereoisomers of NANM and ifenprodil) which, like phencyclidine, are known to antagonise the actions of N-methyl-D-aspartate (NMDA), would produce similar effects. When rats received injections of these compounds, after consuming a novel solution of saccharin, their subsequent consumption of the same solution decreased. The smallest doses of the different drugs which induced clear taste aversions were: phencyclidine 3 mg/kg, MK-801 0.3 mg/kg, (+)-NANM 10 mg/kg, (-)-NANM 3 mg/kg and ifenprodil 10 mg/kg. Thus, all the drugs were active. However, as neither the potencies nor the efficacies of the different compounds in inducing taste aversions correlated with their other behavioural effects or with their relative potencies in antagonising the effects of NMDA or in displacing phencyclidine from its binding sites, the mechanisms involved are unclear.

Adrenergic alpha-Antagonists↗

Malrotation and midgut volvulus presenting as malabsorption.

Volvulus of the midgut associated with intestinal malrotation classically presents in early life with complete, or intermittent, high intestinal obstruction. We describe the case of a boy presenting at 16 months of age with a history of malabsorption and failure to thrive. The importance of considering this rare diagnosis in such cases is discussed.

Humans↗

Reduction of ocular lens dosage in dacrocystography.

Irradiation of the lens of the eye in dacrocystography is largely avoidable. We have measured the lens dosage in bilateral dacrocystography in vivo and in a phantom. We describe simple protective measures which can reduce the lens dosage by over 95% to less than one mGy.

Humans↗

The role of the subthalamic nucleus in experimental chorea. Evidence from 2-deoxyglucose metabolic mapping and horseradish peroxidase tracing studies.

In previous studies we have shown that hemichorea can be induced in the conscious monkey by localized injection of gamma-aminobutyric acid (GABA) antagonists into the contralateral lentiform complex. It has been argued that the primary site of drug action in inducing chorea is the lateral segment of the globus pallidus. In the present study, the neural mechanisms which underlie this experimental dyskinesia were investigated by two separate approaches. First, the efferent projections of the lentiform complex were mapped using neuroanatomical tracing techniques. This involved injecting horseradish peroxide into sites which had previously given chorea when injected with the GABA antagonist bicuculline. Secondly, the 2-deoxyglucose (2-DG) metabolic mapping technique was applied to animals during active dyskinesia. This procedure permitted the autoradiographic measurement of local cerebral glucose uptake which was used as an index of regional synaptic activity. In both instances, the strongest labelling was seen in the dorsolateral region of the subthalamic nucleus. On the basis of this finding it is suggested that the pallidosubthalamic pathway plays a crucial role in the mediation of experimentally-induced chorea. Specifically, the pallidosubthalamic pathway arising from the lateral pallidal segment is abnormally overactive, which causes physiological inhibition of the subthalamic nucleus. The pattern of 2-DG uptake in the medial segment of the globus pallidus and thalamus was similar to that seen in animals with experimentally-induced ballism. This similarity is interpreted as suggesting that a common neural mechanism underlies both experimentally-induced chorea and ballism.

Animals↗