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Biomedical subjects

J Ball

Publications and source records attributed to J Ball.

At least 91 records · Page 5Linked to original sources

Two new IgA1-kappa plasma cell leukaemia cell lines (JJN-1 & JJN-2) which proliferate in response to B cell stimulatory factor 2.

Two new cell lines with the phenotype of terminally differentiated B cells have been derived from the presentation bone marrow of a patient with plasma cell leukaemia. They express the same immunoglobulin (A1-kappa) as the original bone marrow cells. JJN-1 is an hypodiploid, slow-growing line with a plasmacytic morphology, which grows in medium with 15-20% fetal calf serum. When JJN-1 was stimulated with a supernatant ('ESG') containing B cell stimulatory factor 2 (BSF-2/IL-6), a hypotetraploid sub-line, JJN-2, was selectively stimulated. JJN-2 is dependent on ESG for survival. The stimulatory effect of ESG can be completely abrogated by an anti-BSF-2 monoclonal antibody. However, purified BSF-2 alone only produces sub-maximal stimulation of the lines. Both lines show complex karyotypic abnormalities, including 14q- and del(6q). JJN-1 and JJN-2 may be useful for the study of late B cell differentiation and for use as immunogens for the generation of anti-plasma cell monoclonal antibodies.

Antigens, Surface↗

A comparison of the distributions of eight peptides in spinal cord from normal controls and cases of motor neurone disease with special reference to Onuf's nucleus.

The distributions of 8 peptides were studied in the 4 major segmental levels (cervical, thoracic, lumbar, sacral) of the spinal cord in 52 neurologically normal cases. Similar regions from 36 cases of motor neurone disease (MND) were compared using the same procedures to determine possible changes in the distribution of peptides in areas associated with sensory, motor and autonomic function. In normal spinal cords, calcitonin gene-related peptide (CGRP)-, the C-flanking peptide of neuropeptide Y (CPON)-, enkephalin-, galanin-, neurokinin-like-, somatostatin- and vasoactive intestinal polypeptide (VIP)-immunoreactive fibres were abundant in the dorsal horn. Numerous somatostatin-immunoreactive cell bodies were also present. In the ventral horn, immunoreactive fibres were less abundant. Most motoneurones were closely apposed by fibres immunoreactive for enkephalin, neurokinin, somatostatin and thyrotrophin-releasing hormone (TRH). A subpopulation of motoneurones, most notable in lumbar segments, displayed CGRP immunoreactivity. In common with autonomic nuclei, Onuf's nucleus, which is thought to innervate perineal striated muscle and external urethral and anal sphincters, was densely innervated with CPON-, enkephalin-, and in particular somatostatin-immunoreactive fibres, thus suggesting Onuf's nucleus may have an autonomic component. In the diseased cords, there was a reduction in the area of the ventral horn and numbers of motoneurones as revealed by conventional histological staining and immunostaining of neurofilament triplet proteins. No changes in the distribution of peptides was noted in the dorsal horn or autonomic nuclei. By contrast, in the ventral horn, neurokinin-, enkephalin-, somatostatin- and TRH-immunoreactive fibres, which are normally found associated with motoneurones, were absent. Therefore, not only are motoneurones lost in MND, but also the fibres which innervate them. CGRP-immunoreactive motoneurones were not observed, a finding consistent with the proposed role of this peptide as a muscle-trophic factor. In contrast to the large motoneurone groups in the ventral horn, the neuronal integrity of Onuf's nucleus and the peptides associated with it were spared. These data further imply that Onuf's nucleus is not a typical motor nucleus and it is not purely somatic. The coincident loss of peptide immunoreactivity and motoneurones from the large motor nuclei and sparing of Onuf's nucleus and its peptide-containing constituents in the diseased state suggests that peptides contribute to maintenance of neural integrity.

Adolescent↗

Doppler flow velocity mapping in an in vitro model of the normal pulmonary artery.

Pulsed Doppler pulmonary artery velocity measurements are useful in evaluating a number of cardiac conditions including pulmonary hypertension, pulmonary stenosis and insufficiency, intracardiac shunts and other congenital abnormalities. However, variations in sample location relative to the arterial wall and valve have been thought to affect pulmonary artery velocity and acceleration measurements clinically. Therefore, pulsed Doppler and color flow mapping were performed in a pulsatile flow apparatus connected to a glass or Plexiglas model of the main pulmonary artery and its bifurcation, which contained a Hancock 29 mm pericardial tissue valve (5.35 cm2 orifice). Doppler sample volumes were placed at four sites: 1) at the pulmonary valve leaflet tips, centrally; 2) 2 cm distal to the leaflet tips, centrally; 3) 2 cm distal but laterally near the pulmonary artery wall; and 4) at the pulmonary artery bifurcation, centrally. Doppler peak flow velocity and acceleration time were measured. There was no difference between sites 1 and 2 in peak flow velocity or acceleration time. At site 3, peak flow velocity and acceleration time were both less than at site 1 (mean +/- SD, 85 +/- 44 versus 105 +/- 39 cm/s, p less than 0.005, and 162 +/- 65 versus 188 +/- 46 ms, p less than 0.03, respectively). Moreover, the pulmonary artery velocity contour at site 3 exhibited increased spectral dispersion and notching and increased variance on the color spectrum. At site 4, peak flow velocity was less than at site 1 (85 +/- 31 versus 105 +/- 39 cm/s, p less than 0.005), whereas pulmonary artery acceleration time was not significantly different. In this model, Doppler pulmonary artery flow velocity was best recorded within 2 cm of the valve and in the center of the vessel. Similar studies should be performed in the human pulmonary artery to standardize the recording technique and sample sites for Doppler measurements of velocity and acceleration.

Blood Flow Velocity↗

An analysis of myeloma plasma cell phenotype using antibodies defined at the IIIrd International Workshop on Human Leucocyte Differentiation Antigens.

Fresh bone marrow from 43 cases of myeloma and three cases of plasma cell leukaemia has been phenotyped both by indirect immune-rosetting and, on fixed cytospin preparations, by indirect immunofluorescence. Both clustered and unclustered B cell associated antibodies from the IIIrd International Workshop on Human Leucocyte Differentiation Antigens were used. The results confirm the lack of many pan-B antigens on the surface of myeloma plasma cells, i.e. CD19-23, 37, 39, w40. Strong surface reactivity is seen with CD38 antibodies and with one CD24 antibody (HB8). Weak reactions are sometimes obtained with CD9, 10 and 45R. On cytospin preparations CD37, 39 and w40 are sometimes weakly positive, and anti-rough endoplasmic reticulum antibodies are always strongly positive. Specific and surface-reacting antiplasma cell antibodies are still lacking.

Antibodies, Monoclonal↗

Changes in the factor VIII complex in diabetic ketoacidosis: evidence of endothelial cell damage?

Factor VIII-related antigen and von Willebrand factor are synthesised by and released from vascular endothelium. Acute increases in the plasma concentration of these proteins may reflect endothelial cell damage. We have thus measured the plasma concentration of factor VIII-related antigen and von Willebrand factor, together with procoagulant factor VIII, during the course of acute diabetic ketoacidosis in seven patients. In addition, evidence for qualitative changes in the factor VIII complex was sought. Plasma factor VIII-related antigen and von Willebrand factor were markedly increased (plasma factor VIII-related antigen at presentation, median 2.75 U/ml; von Willebrand factor 2.95 U/ml) and returned toward normal with clinical and biochemical resolution (plasma factor VIII-related antigen at clinical recovery, median 1.80 U/ml; von Willebrand factor 2.05 U/ml). Plasma procoagulant factor VIII followed a similar pattern, but levels were less elevated (plasma procoagulant factor VIII, at presentation, median 1.6 U/ml; at clinical recovery, 1.2 U/ml). Crossed immunoelectrophoresis and sodium dodecyl sulphate-acrylamide electrophoresis with autoradiographic identification of multimeric structure revealed no evidence of structurally abnormal factor VIII-related antigen in diabetic ketoacidosis. However, an extra peak on crossed immunoelectrophoresis ("pre-peak") was a feature in the acute phase ketoacidotic plasma in six subjects, and may represent aggregated factor VIII. Changes in plasma factor VIII are a feature of diabetic ketoacidosis and, whilst not specific to this condition, may be the result of endothelial cell damage.

Adult↗

Demonstration of abnormal factor VIII multimers in acquired von Willebrand's disease associated with a circulating inhibitor.

We have studied the factor VIII multimeric structure in four patients with acquired von Willebrand's disease associated with a circulating inhibitor to the factor VIII complex. In three of the four patients tested, the high and medium molecular weights bands were absent when assessed by sodium dodecyl sulphate-agarose electrophoresis. Plasma from the fourth patient contained all the factor VIII multimeric forms, although the high molecular weight bands were markedly decreased in concentration. Intravenous infusion of 1-deamino-(8-D-arginine)-vasopressin (DDAVP) resulted in the appearance of a full complement of multimers in the plasma of the two patients tested. This response was, however, transient and a return to pre-infusion multimeric composition occurred within 2-4 h. In the patients studied, an inhibitor to the factor VIII complex has induced an acquired variant von Willebrand's disease which transiently corrects after the infusion of DDAVP.

Deamino Arginine Vasopressin↗

Amodiaquine induced agranulocytosis: inhibition of colony growth in bone marrow by antimalarial agents.

Bone marrow was cultured in vitro for colonies of granulocytes and macrophages five months after a patient had recovered from amodiaquine induced agranulocytosis. The addition of amodiaquine, chloroquine, and sulfadoxine to the culture was followed by a dose dependent inhibition of colony growth in the patient's marrow but not in normal control bone marrow. Colony growth was, however, unaffected by proguanil, pyrimethamine, and quinine. These findings show that in vitro marrow culture may have important predictive value in some cases of drug induced agranulocytosis.

Adult↗

Steady flow velocity measurements in a pulmonary artery model with varying degrees of pulmonic stenosis.

Velocity and flow visualization studies were conducted in an adult size pulmonary artery model with varying degrees of valvular stenosis, using a two dimensional laser Doppler anemometer system. Velocity measurements in the main, left and right branches of the pulmonary artery revealed that as the degree of pulmonic stenosis increased, the jet type flow created by the valve hit the distal wall of the LPA farther downstream from the junction of the bifurcation. This in turn led to higher levels of turbulent and disturbed flow, and larger secondary flow motion in the LPA compared to the RPA. The high levels of turbulence measured in the main and left pulmonary arteries with the stenotic valves, could lead to the clinically observed phenomenon of post stenotic dilatation in the MPA extending into the LPA.

Blood Flow Velocity↗

Treatment of the juvenile bunion by Mitchell osteotomy.

Twelve patients who had a total of 18 Mitchell bunionectomies were reviewed to assess the long-term results of the procedure. Although metatarsus varus correction was maintained in all cases, hallux valgus recurred in 11 of the 18 cases. Sixty-seven percent reported complete relief or improvement of preoperative pain. Although lateral metatarsalgia did occur, the most common area of persistent pain remained the first metatarsal. Six of 18 procedures had marked loss of active joint motion, associated with pain and an unsatisfactory result. Of 18 procedures, 11 (61%) were satisfied with the results of their osteotomy. Although the Mitchell osteotomy corrected the metatarsus primus varus in each case, the current series shows a discouraging incidence of later recurrence of hallux valgus and restriction of metatarsophalangeal motion causing the abandonment of this procedure for the management of juvenile bunion.

Adolescent↗

A clinical and ultrastructural study of osteogenesis imperfecta after flavonoid (Catergen) therapy.

A trial of the flavonoid Catergen (Zyma) has been undertaken in 11 adults with osteogenesis imperfecta (Ol). The only significant clinical or metabolic side-effects were severe headaches, which necessitated the withdrawal of 3 patients from the trial. Patient compliance in terms of palatability of Catergen was good, and 3 of the 8 patients who completed the trial experienced subjective improvement. After 6 months' treatment with Catergen, the abnormally narrow collagen fibrils found in the osteoid region in a pretreatment bone biopsy specimen from a middle-aged man with the common type 1 (autosomal dominant) form of Ol showed a significant reversion to normal diameters. Post-treatment specimens from his 2 affected sons, who exhibited the same defect, showed a similar but less marked response.

Adult↗

Vertebral rim lesions in the dorsolumbar spine.

The frequency, distribution, and histological characteristics of vertebral rim lesions have been studied at D11 and L4 in 117 post-mortem spines in subjects aged 13-96 years. Only one lesion was found in patients less than 30 years, but thereafter the frequency increased with age. At least one rim was affected in the majority of patients greater than or equal to 50 years. They were found more frequently in the upper than the lower rim and they were also more common anteriorly than posteriorly. Lesions were associated with focal avulsion of the annulus in an otherwise healthy disc or with annular tears running into the rim. Rim lesions can be recognised radiographically by the presence of the vacuum phenomenon, vertebral rim sclerosis with or without a cup-shaped defect in the rim and osteophytes confined to one side of the disc. The histological appearances suggest a traumatic aetiology, and since bone is known to be supplied with pain sensitive nerve endings the lesions may be important in the general context of low back pain.

Adolescent↗