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Biomedical subjects

R Lim

Publications and source records attributed to R Lim.

At least 19 recordsLinked to original sources

Polyclonal antibody localizes glia maturation factor beta-like immunoreactivity in neurons and glia.

A rabbit polyclonal antibody (91-01) was raised against recombinant human glia maturation factor beta (r-hGMF-beta). The antibody did not cross-react with a number of other growth factors on ELISA test. When compared with the monoclonal antibody G2-09 previously obtained, 91-01 immunoblotted the same protein band in rat brain extract. However, unlike G2-09 which immunostained only astrocytes and Bergmann glia, 91-01 stained neurons as well. Many but not all neurons in the central and peripheral nervous system were positive for GMF-beta. The larger cell population stained by the polyclonal antibody was most likely due to its increased sensitivity, although other explanations are possible. The presence of GMF-beta-like immunoreactivity in both neurons and glia raises the possibility of a wider range of cell-cell interaction than was previously considered.

Animals

Effect on prognosis of abolition of exercise-induced painless myocardial ischemia by medical therapy.

During exercise radionuclide ventriculography, many patients with coronary artery disease exhibit painless myocardial ischemia defined as an abnormal left ventricular ejection fraction response without accompanying angina. To see if complete suppression of such exercise-induced painless ischemia by anti-ischemic medication implies a better prognosis in medically treated coronary artery disease, 34 patients underwent repeat testing at 4 weeks receiving regular conventional therapy that rendered angina no worse than class I. With such therapy, painless ischemia was abolished in 12 patients (group I) and persisted in 22 (65%, group II). Both groups were similar in age, number of diseased vessels, proportion with previous myocardial infarction, exercise ejection fraction, and degree of exercise-induced painless ischemia at baseline. At 9 months, adverse events had occurred in 11 patients (2 patients with myocardial infarction, 4 with unstable angina, 2 with angioplasty and 3 with bypass surgery). Only 1 of 12 patients (8%) in group I had experienced events compared with 10 of 22 (45%) in group II (chi-square, 5.4; p less than 0.025; 95% confidence interval, 12 to 61%). Thus, the relative risk of adverse events in patients whose painless ischemia was abolished was only 18% of that in patients in whom it was persistent. These results suggest that (1) the abolition of exercise-induced painless ischemia by conventional symptom-dictated medical therapy confers a better short-term prognosis in medically treated coronary artery disease, and (2) therapeutic efficacy may need to be assessed by titration against ischemia and not against angina.

Adult

High-risk coronary angioplasty with elective intra-aortic balloon pump support.

Percutaneous transluminal coronary angioplasty was attempted with elective percutaneous intra-aortic balloon pump support in 21 patients (mean age 60 years, range 40-82; 18 males) with unstable angina (n = 2), multivessel coronary disease requiring multivessel angioplasty (n = 2), severe left ventricular dysfunction (ejection fraction 10-30%; n = 16) or ventricular fibrillation at diagnostic angiography (n = 1). Fourteen patients had 3-vessel disease (1 with vein grafts also diseased), 6 had 2-vessel disease and 1 had isolated left anterior descending disease. Twenty-five procedures were performed (one in 18 patients, two in 2 patients and three in one patient) on 42 lesions in 34 vessels/grafts. There was no angioplasty-related death. Successful dilatation was achieved in 38/42 lesions (90%) in 21/25 procedures (84%) without major complication. Three procedures were complicated: one by major coronary dissection without sequelae, one by haemodynamic deterioration due to distal occlusion and one by an unstable residual stenosis in the attempted vessel necessitating urgent bypass surgery. The only complication related to the intra-aortic balloon pump was local haematoma in 2 patients. In conclusion, elective intra-aortic balloon pump support may be safely used to stabilise high-risk patients undergoing coronary angioplasty, leading to a satisfactory primary success rate.

Adult

Benign mesodermal tumors producing nasal deformity.

Tumors of neurogenic (ectodermal) origin are well-described causes of nasal deformity. We present a patient with a benign mesodermal tumor (unclassified spindle cell) producing nasal deformity. A retrospective review of the two senior authors' records provided an additional three patients with nonvascular benign mesodermal nasal masses (fibroma and leiomyoma). Benign mesodermal masses can occur in the midline of the nose and need to be differentiated from dermoids and gliomas. Misdiagnosis is the rule. Excisional biopsy is required for definitive diagnosis. In addition, excisional biopsy is curative and can help to minimize the subsequent nasal deformity if performed early in the disease process. Immunohistochemical and electron microscopy may be required for comprehensive diagnosis and treatment.

Adult

Interaction of acidic fibroblast growth factor and transforming growth factor-beta in normal and transformed glia in vitro.

The mitogenic and morphological effects of acidic fibroblast growth factor (aFGF) and transforming growth factor-beta (TGF-beta) were assessed on cultured fetal rat astrocytes and C6 rat glioma cells in the presence and absence of serum. Astrocytes incubated with aFGF exhibited an increase in mitotic activity and characteristic morphological changes involving extensive process formation and rounding of cell bodies. Astrocytes incubated with TGF-beta underwent a slight decrease in mitotic activity and remained morphologically unchanged. Cells exposed to a combination of aFGF and TGF-beta demonstrated an attenuation of both the mitogenic and morphological changes observed in the presence of aFGF alone. The C6 glioma cells cultured in the presence of aFGF underwent a characteristic morphological change from a rounded piling cell mass to a more spindle-shaped bipolar cell layer, accompanied by an increase in mitotic activity. In contrast to the astrocyte cultures, increased growth and similar morphological effects were produced by TGF-beta. The combination of aFGF and TGF-beta did not result in attenuation of the mitogenic and morphological changes (as seen in astrocytic cells). These results suggest that, in normal fetal rat astrocytes, TGF-beta is capable of attenuating the mitogenic and morphological changes induced by aFGF in vitro. In the transformed C6 glioma cell line, aFGF and TGF-beta elicit similar mitogenic and morphological changes, without evidence of an antagonistic interaction as seen in normal astrocytes.

Animals

Expression of glial fibrillary acidic protein in human medulloblastoma cells treated with recombinant glia maturation factor-beta.

Medulloblastoma, a common pediatric brain tumor, is a primitive neuroectodermal tumor which often displays neuronal and/or glial characteristics. We have investigated the consequences of treating cell lines derived from a human medulloblastoma with glia maturation factor-beta (GMF-beta), a protein found in mammalian brain. GMF-beta promotes growth arrest and morphological alteration of cultured glioma and neuroblastoma cells. The proliferation of medulloblastoma cells was arrested 24-48 hr after exposure to human recombinant GMF-beta. During the same period, treated cells acquired a morphology similar to that of mature astrocytes. By 72 hr, all treated cells bound an antibody against glial fibrillary acidic protein (GFAP), a distinguishing biochemical feature of mature astrocytes. Immunoreactivity was accompanied by de novo expression of GFAP mRNA. Our observations are the first demonstration of the induction of morphological and biochemical characteristics of mature astrocytes in cultured medulloblastoma-derived cells by an exogenous factor.

Cell Division

Glia maturation factor beta stimulates axon regeneration in transected rat sciatic nerve.

Rat sciatic nerves were bilaterally transected and repaired with an entubulation technique. The nerve interstump gap was filled with either collagen gel or collagen gel mixed with a putative neurotrophic factor (leupeptin, 4-aminopyridine, lipid angiogenic factor or glia maturation factor beta (GMF-beta]. Six weeks after nerve transection, the myelinated distal stump axons were quantified for each nerve. Only the nerves treated with GMF-beta had significantly more axons than the control side.

Animals

Early prognosis after thrombolysis: value of exercise radionuclide ventriculography performed on anti-ischaemic medication.

We examined the prognostic value of exercise radionuclide ventriculography (RNV) performed on anti-ischaemic medication following thrombolysis. Within 3 months of thrombolysis for first myocardial infarction, 31 medically treated patients with revascularisable but non-critical and minimally symptomatic coronary disease had left ventricular ejection fraction (LVEF) measured by first-pass exercise RNV. This was first performed off treatment and then repeated within 4 weeks on patients' regular medication. Follow-up at 12 months post-thrombolysis showed that 5 patients (Group I) had suffered significant recurrent symptoms (worsening angina requiring revascularisation in 3, unstable angina in 1, reinfarction in 1), but 26 remained well (Group II). Both groups were similar in age, post-thrombolytic severity of coronary disease, exercise LVEF whether off (39% vs 43%) or on medication (43% vs 44%), and change in LVEF with exercise ([symbol: see text]LVEF) off medication (-11% vs - 3%). However, on medication, there was a significant difference in mean [symbol: see text]LVEF between Groups I and II (-11% vs + 5%, P = 0.0008, 99% confidence interval = 4 to 26%). Thus, following thrombolysis, an abnormal [symbol: see text]LVEF despite anti-ischaemic medication may identify patients at risk of significant early recurrent ischaemia. Post-thrombolysis prognostic testing by exercise RNV may therefore be of greater value when performed on rather than off medication.

Adult

Molecular cloning and expression of biologically active human glia maturation factor-beta.

Glia maturation factor-beta, a protein found in the brains of all vertebrates thus far examined, appears to play a role in the differentiation, maintenance, and regeneration of the nervous system. Using oligonucleotide probes based on the sequences of three tryptic peptides derived from bovine glia maturation factor-beta, we screened a human brainstem cDNA library in lambda gt11. A 0.7-kb clone was isolated, sequenced in its entirety, and found to encode a polypeptide of 142 amino acids which contained regions identical to the three bovine peptides. This polypeptide, human recombinant glia maturation factor-beta, has been expressed in Escherichia coli and found to possess structural characteristics and biological activity indistinguishable from those of the native bovine protein.

Amino Acid Sequence

Bradyarrhythmias in acute myocardial infarction: should thrombolysis lower the decision threshold for temporary pacing?

Both acute myocardial infarction and reperfusion therapy with thrombolytic agents may be associated with bradyarrhythmias, and there may be a case for 'prophylactic' insertion of a temporary pacing wire in selected patients. We describe 4 patients in whom clinical decisions had to be made concerning the appropriateness and timing of temporary pacing, and discuss the implications for modern guidelines on the indications for pacing in such a setting.

Bradycardia

Bronchial reactivity in patients undergoing long-term haemodialysis for chronic renal failure.

Trapping of neutrophils within the lung occurs in patients undergoing haemodialysis and is also a possible mechanism in the pathogenesis of bronchial hyper-responsiveness. Falls in peak expiratory flow rate occur in most dialysis patients, and some develop overt asthmatic symptoms. To see whether these changes in airway function are secondary to increases in bronchial reactivity during haemodialysis, we therefore performed histamine challenge testing in 6 non-asthmatic patients before and after haemodialysis. No change in reactivity was observed, suggesting that haemodialysis does not commonly result in bronchial hyper-reactivity in non-asthmatic individuals.

Adult