Biomedical subjects

B S Ooi

Publications and source records attributed to B S Ooi.

At least 37 records · Page 2Linked to original sources

PubMed1999

Transpelvic rectus abdominis flap for perineal reconstruction following abdominal perineal resection with en bloc partial cystectomy and prostatectomy for locally advanced rectal cancer.

We report a case of locally advanced carcinoma of the rectum invading the bladder and prostate in a young man treated initially with neoadjuvant chemoradiotherapy. This was followed by an en bloc resection of the tumour, partial cystectomy and prostatectomy and an abdominal perineal resection. The urinary bladder was reconstructed and a new bladder neck reimplanted into the proximal urethra where the sphincter had been preserved. There was extensive radiation changes to the perineal skin where a wide excision had been performed. The pelvic defect was reconstructed with a pedicled transpelvic rectus abdominis myocutaneous flap. The patient recovered uneventfully and remains well with no clinical evidence of recurrence 18 months post-operatively. In very selected cases there is a definite role for neoadjuvant therapy and enbloc resection of the tumour followed by reconstruction of the perineum.

Adult↗

PubMed1998

Stimulation of endothelial cell production of vasoconstrictive substances by hypertensive sera.

The endothelial cell regulates vessel tone by elaborating a number of vasoactive substances such as thromboxane and endothelin, both of which are highly vaosconstrictive, and prostacyclin and nitric oxide, both of which are vasodilatory. The current study examines the postulate that one of the mechanisms responsible for the increased vessel tone found in hypertension is the presence of substances in the sera of patients with this disorder that stimulates selectively the endothelial cell production of thromboxane and endothelin. Sera from ten patients with mild hypertension and from 11 age-matched controls were incubated with human umbilical arterial endothelial cells and the concentrations of endothelin, thromboxane, prostacyclin, and nitric oxide produced by the cells was measured in the supernatant. The results of the assays showed that the amounts of thromboxane and endothelin produced by endothelial cells in response to stimulation by hypertensive sera were significantly higher than the amounts produced in response to control sera; in comparison, the amounts of prostacyclin and nitric oxide produced by the cells in response to either hypertensive sera or control sera were not significantly different. The findings suggest that a mechanism that may be responsible for the increased vascular tone found in hypertension is the presence of substances in hypertensive sera that stimulate endothelial cells selectively to produce increased amounts of the vasoconstrictive hormones, endothelin and thromboxane.

6-Ketoprostaglandin F1 alpha↗

PubMed1998

Role of insulin-like growth factor-I (IGF-I) receptor, IGF-I, and IGF binding protein-2 in human colorectal cancers.

The identification of novel autocrine/paracrine signaling pathways and possible markers represents an important component in the understanding of tumor growth control. In this study, we assessed the potential role of insulin-like growth factor-I (IGF-I), the IGF-I receptor (IGF-IR) and IGF binding protein-2 (IGFBP-2) in human colorectal cancer. Initial studies demonstrating increased IGF-I binding and IGF-IR density in human colon cancer tissue revealed that a component of iodinated (3-[125-I]iodotyrosyl) IGF-I (125I-ICGF-I) binding was not attributable to IGF-IR. Binding studies and Western blot analysis suggested that this second component of 125I-IGF-I binding could be due to IGFBP-2. Further analysis by a specific solution hybridization/RNase protection assay for IGF-IR mRNA levels, IGFBP-2 mRNA levels and in situ hybridization for IGFBP-2 localization, was carried out in nine patients with colon cancer. IGF-IR mRNA levels by RNAse protection assays were unchanged, whereas IGFBP-2 mRNA levels were increased 4-8-fold in patients with colon cancer compared to controls. Three patients with Dukes stage C disease had the highest levels of IGFBP-2 mRNA. In situ hybridization studies localized IGFBP-2 mRNA to malignant cells and not to the surrounding stromal cells, suggesting an autocrine role for IGFBP-2. The discrepancy between increased IGF-I binding, IGF-IR density, IGFBP-2 mRNA and the minimal modulation of the IGF-IR mRNA implies post-transcriptional regulation of IGF-IRs. Our results suggest that IGFBP-2 may be implicated in colon cancer metastases and prognosis. Its usefulness as a potential tumor marker should be further investigated.

Autoradiography↗

PubMed1998

Management of anorectal foreign bodies: a cause of obscure anal pain.

BACKGROUND: Few patients with anorectal foreign bodies will freely admit to transanal introduction. The results of long-term follow-up in these patients have been sparse. METHODS: Data from April 1989 to April 1997 were extracted from a prospective computerized database. The clinical features and the results of a departmental management protocol for anorectal foreign bodies were analysed. In addition, long-term outcomes were obtained by telephone interview. RESULTS: Thirty patients (25 men, 5 women) with a mean age of 46 (range 16-72) years) were treated for this condition. While 10 patients (33.3%) admitted to transanal insertion, the remaining 20 (66.7%) complained of anal pain. Among the latter, the foreign body was subsequently found on routine digital rectal examination in nine patients (45%), on X-ray in nine (45%) and it was passed out unexpectedly after fleet enema in two (10%). Factors which raised suspicion for X-rays included atypical gender behaviour, lax anal sphincters and bloody or mucoid rectal discharge. Transanal recovery was successful with sedation in 12 (40%), general anaesthesia in 13 (43.3%), and laparotomy was needed in three (10%; which included one perforated bowel at presentation). There were two complications (6.7%; one minor rectal abrasion and one bronchopneumonia). There was no long-term faecal incontinence or re-impaction of foreign bodies at 63 (range 8-96) months of follow-up. CONCLUSIONS: Foreign bodies should be suspected in patients with obscure anal pain. Judicious transanal extraction under sedation or general anaesthesia was usually successful with minimal short- and long-term complications.

Adolescent↗

PubMed1996

Differential effects of costimulator signals and interleukin-2 on T cell receptor-mediated cell death of resting and activated CD4+ murine splenic T cells.

Postthymic T cell receptor (TCR)-mediated cell death offers the potential for creating antigen-specific transplant tolerance analogous to thymic clonal deletion. Murine specific CD4+ cell were rigorously purified by: (a) adherent cell depletion and (b) magnetic bead/monoclonal antibody (mAb) depletion of macrophages, Ia+ cells, mu-chain+ cells, NK cells, and CD8+ T cells. CD4+s were typically > 95% pure by flow cytometry. Resting CD4+s stimulated by plastic-immobilized anti-TCR/CD3 mAb wee shown to die in the absence of exogenous interleukin (IL)-2. Blasting CD4+s showed dose-dependent cell death upon religation of TCR/CD3 in the presence of IL-2; however, withdrawal of IL-2 from blasting CD4+s also resulted in cell death. Cell death was shown to be apoptotic by flow cytometry DNA content analysis. Anti-CD28 mAb, co-immobilized with anti-TCR/CD3 mAb, inhibited cell death of resting CD4+s in the absence of exogenous IL-2; however, anti-CD28 mAb showed minimal cell death inhibition of CD4+ blasts when TCR/CD3 was religated. In contrast, splenic adherent cells effectively inhibited cell death of blasting CD4+s induced by TCR/CD3 mAb religation. We conclude that TCR-mediated programmed cell death of highly purified splenic CD4+s is dependent upon activation state, availability of IL-2, and accessory cell or CD28 costimulator signals. Furthermore, IL-2 acts to protect against cell death in both resting and activated CD4+ T cells. IL-2 protection could be overcome by high concentrations of anti-TCR/CD3 mAb, which results in cell death of CD4+ blasts. In the effort to understand potential mechanisms of peripheral tolerance induction, these findings assist to distinguish and define conditions for antigen receptor-mediated programmed cell death of mature CD4+ T cells.

Animals↗

PubMed1996

Hyperglycemia augments macrophage growth responses to colony-stimulating factor-1.

Pathologic changes produced (or potentiated) by the diabetic state include diabetic retinopathy, nephropathy, and atherosclerosis. There is evidence that the macrophage is implicated in the pathogenesis of these lesions. One of the growth factors known to exert a profound influence on macrophage physiology is colony-stimulating factor-1 (CSF-1). CSF-1 has previously been shown to be produced by endothelial cells, mesangial cells, and vascular smooth muscle cells, and it is reasonable to suggest that the interaction of this factor on infiltrating macrophages is an event that may have pivotal importance in the formation of diabetic lesions. We report on the modulating influence of hyperglycemia on the proliferative response of mouse splenic macrophages to CSF-1. Our studies showed that hyperglycemia enhanced the growth response of such macrophages to CSF-1. The mechanism underlying this enhanced response was examined, and it was demonstrated that hyperglycemia induced a threefold increase in CSF-1 receptor (CSF-1r) mRNA expression as visualized by Northern blot analysis. These investigations provide insight into one of the molecular mechanisms potentially relevant to the genesis of diabetic lesions in the host.

Animals↗

PubMed1996

Demonstration of endothelial-activating properties of hypertensive sera.

Sera from patients with hypertension were examined for their ability to influence endothelial cell function. Sera from 10 patients with hypertension and from 11 age-matched controls were incubated with endothelial cells and their effect on cell growth assessed by endothelial cell 3H-thymidine uptake. Sera from patients with hypertension had a more pronounced stimulatory effect on endothelial cell proliferation than control sera. In addition, hypertensive sera were also examined for their capacity to stimulate endothelial cell production of the vasoactive peptide endothelin. Confluent monolayers of endothelial cells were incubated with sera and the amount of endothelin generated in the supernatant measured by an immunoassay. Amounts of endothelin produced by the endothelial cells in response to hypertensive sera were significantly higher compared with the amounts produced in response to normal sera. The results of the studies suggest that a serum factor(s) in hypertensive patients may be of importance in modulating endothelial cell function. Such a factor(s) may have a significant role in the pathogenesis of hypertension.

Aged↗

PubMed1996

Biology of the mesangial cell in glomerulonephritis--role of cytokines.

The mesangial cell occupies a central position in the genesis of the pertubations occurring during the pathogenesis of glomerulonephritis. In vitro studies have shown that this cell is a metabolically active cell producing a variety of cytokines which act as autocoids; such cytokines are also liberated by the monocytes/macrophages which infiltrate the glomerulus in nephritis. This review summarizes the evidence for the participation of these cytokines in animal models of nephritis and in human renal disease, focusing on the roles of basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, colony-stimulating factor-beta, tumor necrosis factor, interleukin-1, and interleukin-6.

Animals↗

PubMed1995

Modulation of macrophage proliferation by hyperglycemia.

Macrophages have been show to be of importance in three areas of pathology in the diabetic state: (a) in the destruction of the beta cells of the pancreas; (b) in the pathogenesis of the microvascular lesions; and (c) in the atherosclerotic lesion which is a common complication of diabetes. However, there is only scanty information on the behavior of the macrophage in the hyperglycemic environment. The present study investigates the growth of WEHI-3 monocytes/macrophages and the proliferative response of splenic macrophages to colony stimulating factor-1 when cultured in media containing high glucose concentrations. The results of the study show that hyperglycemia increases the proliferation of these macrophages; this effect is not mediated by the effect of osmolality since mannitol and L-glucose failed to produce a similar result. These findings suggest that alterations of macrophage physiology may be an important component of the diabetic state; such alterations may have a role in the production of some of the lesions found in diabetes mellitus.

Animals↗

PubMed1995

Regulation of macrophage growth responses to colony-stimulating factor-1 by 1,25-dihydroxyvitamin D3.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has previously been shown to affect the biology of a variety of immune cells, including the functions of macrophages. The effect of the vitamin D metabolite on the proliferative responses of macrophages to the cytokine colony-stimulating factor-1 (CSF-1) has been studied. It was found that this substance was able to suppress the growth responses of macrophages to CSF-1 as assessed by macrophage-tritiated thymidine uptake and also by cell counts. The effect was specific to this vitamin D metabolite because another vitamin D analogue, 25 hydroxyvitamin D3, did not have a similar effect on the responses of such cells to CSF-1. The results yield information on the regulatory role of 1,25(OH)2D3 on macrophage growth. It would appear that this vitamin D metabolite may act as a negative autoregulatory cytokine because it is produced by the macrophage when it is activated. A schema can be envisaged where CSF-1 is delivered to the macrophage to activate it and to cause it to proliferate. In the process, it also secretes 1,25(OH)2D3, which exerts a suppressive action to dampen this response.

Animals↗

PubMed1995

Host immune deficiency in immune complex nephritis.

Evidence is reviewed that indicates that an immune deficiency state may underlie patients with immune complex nephritis. Studies in several laboratories provide data that show defective immune function in patients with nephritis at the following loci: defective immunoglobulin production, impaired monocyte Fc and C3b receptor function, diminished complement biosynthesis, and decreased mesangial cell colony-stimulating factor-1 biosynthesis. Aberrant monocyte function may be an important common denominator. The validation of this hypothesis has important implications for therapeutic strategies.

Animals↗

PubMed1993

Responses of mesangial cells of autoimmune mice to cytokines.

Glomerulonephritis is one of the most important complications of SLE. The genesis of the renal lesions in this disorder is determined by a cascade of events that leads to mesangial cell proliferation as one of the hallmarks of the kidney disease. The current study examines the postulate that there may be intrinsic abnormalities in the mesangial cells of the autoimmune host which predisposes it to develop nephritis. It investigates the possibility that growth responses of mesangial cells of the autoimmune MRL/MpJ-lpr/lpr mice are different from those of their congenic normal MRL/MpJ-(+)/+ (MRL-(++)) counterparts when cultured with various cytokines. To test this possibility, growth responses of mesangial cells as assessed by [3H]TdR uptake were measured when these cells were cultured with epidermal growth factor, platelet-derived growth factor, transforming growth factor-beta, and 1,25-dihydroxy vitamin D3. Epidermal growth factor stimulated the growth of mesangial cells of both strains of mice equally, but platelet-derived growth factor appeared to elicit a more pronounced proliferative response from mesangial cells of the autoimmune mice. In regard to inhibitory substances tested, mesangial cells of autoimmune MRL-lpr mice appeared to be relatively insensitive to the suppressive effects of transforming growth factor-beta and 1,25-dihydroxy vitamin D3. Collectively, the response profile of mesangial cells of the MRL-lpr mice suggests that these cells have a tendency to proliferate when they are acted on by cytokines, so that they may be more susceptible to develop the proliferative lesions seen in the nephritis of SLE.

Animals↗

PubMed1993

Induction of mouse monocyte Ia expression by a mesangial cell-derived product.

Previous studies in many laboratories have shown that macrophage Ia expression is not constitutive but under regulation. We provide data which demonstrate that product(s) of mouse mesangial cell cultures induce blood monocyte Ia expression as demonstrated by immunofluorescence. This process is time-related and is also dependent on novel protein synthesis, being abrogated when the monocytes are pretreated with cycloheximide. Preliminary characterization shows the mesangial cell product to be sensitive to heating at 100 degrees C x 30 min, to be resistant to digestion by trypsin at a concentration of 4 x 10(-6) M, and to have a molecular size of 10-100 kD as established by Amicon ultrafiltration. The substance is not interferon-gamma (IFN-gamma) since cultured mesangial cells had no contaminating T cells, mesangial cell supernatant had no detectable levels of IFN-gamma, and the Ia-inducing activity of the mesangial cell product was not abrogated by incubation of monocytes with mesangial cell supernatant which had been immunoprecipitated with anti-IFN-gamma. Similarly, experiments using anti-CSF-1 have excluded the possibility that the substance is CSF-1. The results of the study have relevance to the mechanisms by which monocytes which take up residence in the glomerular mesangium acquire Ia positivity, and also provide a potentially novel pathway by which a tissue product may induce monocytes to express Ia.

3T3 Cells↗

PubMed1993

Biosynthesis of colony-stimulating factor-1 (CSF-1) by mesangial cells of autoimmune mice.

The amounts of colony-stimulating factor (CSF-1) produced by the mesangial cells of the kidney may be of pivotal importance in determining the outcome of nephritis, since CSF-1 activates macrophages, and macrophages have been shown to perform an important scavenger function in removing immune complexes which localize in the kidney. To test this hypothesis, the present study examined CSF-1 production by mesangial cells of the autoimmune MRL/MpJ-lpr-lpr strain of mice and also of their normal congenic MRL/MpJ-++ counterparts. It was found that mesangial cells of autoimmune mice produced diminished amounts of functional CSF-1 when measured by a bioassay, giving validation to the hypothesis proposed. Of interest, expression of CSF-1 mRNA was discordantly increased in mesangial cells of the MRL-lpr autoimmune mice. Based on current knowledge of the pathway for CSF-1 synthesis and secretion, it would appear that there may be a block in the post-transcriptional pathway for CSF-1 biosynthesis in autoimmune mesangial cells.

Animals↗

PubMed1991

Evidence that mouse mesangial cells produce colony-stimulating factor-1.

The contractile mesangial cell has previously been shown to be a metabolically active cell capable of producing a variety of substances. In this communication, we report that the contractile mouse mesangial cell produces a factor which induces the replication of blood monocytes and splenic macrophages but not of peritoneal macrophages. This factor has an isoelectric pH of 4 as determined by chromatofocusing, a molecular weight of 68,000 daltons as determined by gel chromatography, and is reactive to anti-CSF-1 as assessed by experiments showing inhibition of function by the antibody. These physiological, physico-chemical and immunological characteristics indicate that the substance is most likely colony-stimulating factor-1 (CSF-1).

Animals↗

PubMed1990

The biology of mesangial cells in glomerulonephritis.

It is likely that a complex bidirectional interaction occurs between mesangial cells and the immune cells which infiltrate the mesangium during nephritis. Macrophages and other immune cells liberate a series of mediators, including substances such as IL-1, beta-endorphin, TNF, and PDGF--all of which promote the growth of mesangial cells. The end result is mesangial cell proliferation and increased matrix production, both of which are seen in nephritis. The proliferating mesangial cells liberate autocoids such as IL-1 and PDGF, thereby setting up an amplifying loop. Simultaneously, suppressive factors such as TGF-beta are released which antagonize the actions of these growth-promoting substances. The proliferating mesangial cells also produce immunomodulatory peptides, which will in turn act on the infiltrating macrophages to stimulate their replication and activation. Such activated macrophages continue to amplify the inflammatory lesion and also promote the phagocytosis of localized antigen-antibody complexes. The net effect of all of these interactions will depend on the dominance of substances which persist and override the roles of other molecules. Studies of the controls which regulate the production of these growth factors/immune modulators will yield insights into the fundamental mechanisms which determine the outcome in glomerulonephritis.

Animals↗

PubMed1989

1,25-Dihydroxyvitamin D3 and rat vascular smooth muscle cell growth.

Recent studies from several laboratories have shown perturbations of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] metabolism in hypertension. While these perturbations may exert their effect on blood pressure via their actions on calcium metabolism, it is possible that this vitamin D metabolite may have direct effects on vascular smooth muscle cell (VSMC) physiology. To examine this, we studied the effect of 1,25(OH)2D3 on VSMC growth and found that this substance suppressed VSMC [3H]thymidine uptake; furthermore, this vitamin D metabolite also suppressed the stimulatory effect of epidermal growth factor (EGF) on VSMC proliferation. The concomitant presence of this substance appeared to be required for its action on VSMC growth since cells pretreated with the vitamin D metabolite for up to 72 hours and then washed of the substance grew normally and responded to EGF. Studies were also done to determine if 1,25(OH)2D3 had any effect on the function of EGF receptors on VSMC. Experiments using Iodine-125-labeled EGF showed no differences in the binding of this ligand to VSMC, either untreated or treated with 1,25(OH)2D3, which indicates the effect of the vitamin D metabolite on VSMC growth (when exposed to EGF) was not mediated by an alteration of EGF receptor function. The results of these studies have implications for the pathogenesis of vascular diseases such as hypertension and atherosclerosis.

Animals↗

PubMed1989

The effect of transforming growth factor-beta on mouse mesangial cell proliferation.

The factors which regulate mesangial cell growth are of importance in determining the cellular lesions of nephritis. In this communication, we report that transforming growth factor-beta (TGF-beta) exerts a suppressive effect on mesangial cell 3H-thymidine uptake. Furthermore, TGF-beta antagonizes the mitogenic effect of epidermal growth factor (EGF) on DNA synthesis. The concomitant presence of TGF-beta in the cell cultures is not required for its effect since cells pretreated with the substance and rinsed of it showed suppressed 3H-thymidine uptake and did not respond to EGF. The effect of TGF-beta can also be demonstrated on cells committed to proliferate by the prior addition of EGF. The results of the study have relevance to the mechanisms underlying the histologic lesions of immune-mediated nephritis.

Animals↗