Search PubMed⌕ Search

Biomedical subjects

J Woo

Publications and source records attributed to J Woo.

At least 307 records · Page 17Linked to original sources
PubMed1990

FK506--its influence on anti-class 1 MHC alloantibody responses to blood transfusions.

The influence of FK506 on in vivo alloantibody responses to major histocompatability class 1 antigens was investigated in inbred rat strains, and compared with the effect of cyclosporine. AO rats received transfusions of DA blood on days 0 and 7. From days 0 to 14 the rats also received, daily, either FK506 0.3 mg/kg suspended in saline or dissolved in olive oil, or CsA 10 mg/kg. The administration of FK506 suspended in saline at the time of blood transfusion completely abrogated the development of anti-MHC class 1 alloantibodies as detected by indirect hemagglutination (IHA)* and 51Cr release complement dependent cytotoxicity assays (CDC). Isotyping studies showed that FK506 suspended in saline suppressed IgM production and inhibited the switch to IgG production. Similar responses were seen in CsA-treated animals. In contrast, rats treated with FK506 dissolved in olive oil developed high titers of anti-class 1 alloantibodies. On days 49 and 56 the rats were challenged with further DA blood transfusions given without immunosuppression. In the groups given FK506 suspended in saline or CsA, cytotoxic antibodies did not develop; low titer antibodies were, however, detected by IHA in the animals that had previously received FK506 suspended in saline. The results indicate that FK506, in common with CsA, inhibits anti-class 1 MHC alloantibody production, and at the same time enables the development of tolerance. The vehicle in which FK506 is administered is, however, critical to its efficacy at the low doses used. These results may be of relevance to clinical transplantation as similar antibodies mediate hyperacute renal allograft rejection in man.

Animals↗
PubMed1990

Immunosuppressive activity of FK-506 in rats: flow cytometric analysis of lymphocyte populations in blood, spleen and thymus during treatment and following drug withdrawal.

Rats were immunized systemically with sheep red blood cells (SRBC) and given either FK-506 (1 mg/kg) or drug vehicle by i.m. injection for 7 days. In animals receiving FK-506, there was suppression (87%) of the splenic plaque-forming cell response on day 4 and marked reductions in the serum antibody titre throughout the 3-week period following immunization. Sequential flow cytometric analyses of blood lymphocytes revealed statistically significant attenuation, by FK-506, of the increase in relative numbers of OX-12+ (B) cells between days 4 and 7. Following drug withdrawal, OX-12 values remained elevated, whereas in control animals a decline was observed. These changes were reflected in concomitant increases in the relative numbers of OX-19+ (CD3+), W3/25+ (CD4+) and OX-8+ (CD8+) T cells; however, due to an overall reduction in lymphocytes by day 7, absolute values were not significantly affected compared with controls. The pattern of changes in OX-6+ (MHC class II+) cells in blood was similar to that observed for B cells. FK-506 also suppressed increases in the small proportion of blood-borne OX-40+ (activated CD4+) cells and OX-39+ (interleukin-2 receptor+) cells in the 7 day period following immunization; thereafter values for activation marker expression between treatment and control groups were similar. In the spleen, there were fewer significant differences between FK-506 and control groups in the incidences of cells expressing the above markers. OX-8+ cells, however, were significantly higher in drug-treated animals on day 7, and there were also reductions in the small proportions of OX-39+ and OX-40+ cells when compared with controls. In the thymus, reversible medullary atrophy induced by FK-506 was accompanied on day 7 by increases in the incidence of CD4+ and CD8+ cells and by a concomitant reduction in OX-44+ mature, medullary thymocytes. Two weeks after drug withdrawal, the phenotypic marker expression profile had been restored to normal in blood, spleen and thymus. These data provide new information on the apparent capacity of FK-506 to interfere with T cell maturation and its influence on lymphocyte activation in vivo.

Animals↗
PubMed1990

Influence of FK506 and cyclosporin A on alloantibody production and lymphocyte activation following blood transfusion.

The effect of administration of cyclosporin A (CyA) or the novel macrolide FK506 was investigated in AO rats given DA blood transfusions. CyA (10 mg/kg, orally) or FK506 (1 mg/kg, intramuscularly) administered for 14 days from the time of transfusion effectively inhibited primary anti-MHC class I alloantibody production. This profound inhibitory effect persisted throughout the 2-month investigation period, with little increase in 'secondary' alloantibody production following a challenge injection 28 days after drug withdrawal. Flow cytometric analysis revealed no significant differences in the absolute numbers of W3/25+ (CD4+), OX-8+ (CD8+) or OX-12+ (B lymphocytes), in either the spleen or peripheral blood of transfused compared with normal, untreated animals. However, a small but significant increase in the numbers of splenocytes expressing the activation marker OX-40 (activated CD4+ cells) was observed in transfused animals. Either CyA or FK506 significantly reduced the number of cells expressing OX-39 (interleukin-2 receptors) and OX-40. Treatment of transfused animals with CyA, but not FK506 for 14 days resulted in minor, transient reduction in peripheral blood OX-19+ and W3/25+ cells, while 'sparing' the OX-8+ cells; these changes were not observed in spleens. In contrast, the absolute spleen cell numbers of OX-19+, W3/25+ and OX-8+ cells were significantly reduced in transfused animals given 14 days of FK506 treatment, while the corresponding blood cells were unaffected. Induction of splenic lymphoproliferative responses by the T cell mitogen concanavalin A remained normal in animals receiving transfusion alone or with CyA. In contrast, profound inhibition of mitogenic responses was observed in FK506-treated animals and this inhibitory effect declined gradually following drug withdrawal. No non-specific suppressor cell activity was detected in the spleens of rats given transfusion alone or in CyA or FK506-treated transfused animals.

Animals↗
PubMed1990

The influence of FK-506 and low-concentration ciclosporin on human lymphocyte activation antigen expression and blastogenesis: a flow cytometric analysis.

The influence of FK-506 and ciclosporin (CsA), either alone or in combination, on PHA- and alloantigen-induced human blood lymphocyte transformation was investigated. The concentrations of FK-506 and CsA required to cause 50% inhibition of mitogen-induced thymidine incorporation were 1.0 and 200 ng/ml respectively. Evidence of synergistic inhibition of DNA synthesis was obtained when doses of each drug below these concentrations were combined (FK-506, less than or equal to 0.5 ng/ml; CsA less than or equal to 50 ng/ml). In contrast, FK-506 and CsA failed to inhibit PHA-induced increases in cell size and granularity determined by flow cytometric analysis at 1 and 3 days of culture. Moreover, no significant changes in the expression of the interleukin 2 receptor (IL-2R; CD25), transferrin receptor (TR; CD71) or HLA-DR were observed in terms of percentage positive lymphocytes or mean cell surface membrane fluorescence intensity. In primary mixed lymphocyte cultures, 50% inhibition of thymidine incorporation was obtained with FK-506 and CsA concentrations of approximately 0.25 and 25 ng/ml respectively. Evidence of synergy was obtained when lower doses of each drug were combined (FK-506, less than or equal to 0.1 ng/ml; CsA less than or equal to 2 ng/ml). On their own, these concentrations of CsA were ineffective. In contrast to corresponding PHA-stimulated cells, FK-506-treated alloactivated lymphocytes exhibited reductions in IL-2R, TR and HLA-DR antigen expression, which in the cases of IL-2R and TR were further reduced by combination of FK-506 with low-concentration CsA. These data provide further evidence of the potential of combined low-dosage FK-506 and CsA for the control of human T-cell activation and proliferation in response to allostimulation.

Anti-Bacterial Agents↗
PubMed1990

Treatment of severe orthostatic hypotension with the somatostatin analogue octreotide.

The long-acting somatostatin analogue octreotide was used in a patient with severe orthostatic hypotension resistant to conventional treatment. 0.4 ug/kg octreotide given subcutaneously abolished the postural drop in systolic blood pressure for about four hours and was more effective than a combination of fludrocortisone and pindolol.

Drug Administration Schedule↗
PubMed1990

Risk factors predisposing to stroke in an elderly Chinese population--a longitudinal study.

A cohort of 427 (171 males, 256 females) elderly Chinese aged 60 years and over whose health status had been defined in a previous survey was reexamined after a 30-month period to determine the occurrence of stroke. Subjects who initially had a history of transient ischemic attacks (TIA) and nonrheumatic atrial fibrillation had a greater than 10-fold increased risk of stroke in the subsequent 30 months. Men, smokers, alcohol drinkers, overweight subjects, and diabetics, also had a relative risk greater than one, but this did not reach statistical significance. Hypertensive subjects did not have an increased risk of stroke. It is concluded that the most important risk factors in the elderly predisposing to stroke in the short-term are a history of TIA and atrial fibrillation. Preventive measures against these two conditions may have a greater short-term impact in the elderly in reducing stroke occurrence than modification of other risk factors. Further studies involving larger numbers are needed to confirm these findings.

Aged↗
PubMed1990

A case control study of some hematological and biochemical variables in acute stroke and their prognostic value.

Hematocrit, total white cell and platelet counts, plasma urea and creatinine concentrations were estimated in 291 patients (mean age 70 +/- 12 years) admitted consecutively over a 6-month period to a district general hospital with acute stroke. Urinary albumin/creatinine ratio was also determined in a subgroup of patients during a follow-up visit 3 months after ictus. Results were compared with those from age- and sex-matched community controls. Total white cell count was elevated in all types of stroke compared with values from control subjects. Platelet count, plasma urea and creatinine concentrations were higher and the plasma albumin/globulin ratio was lower among patients with ischemic stroke. Elevated total white cell count, urea and creatinine, which were of prognostic significance, were found to be associated with the severity of stroke as indicated by the Glasgow coma score, and did not have any independent prognostic value. Elevated hematocrit was not shown to be a risk factor and did not have any prognostic significance. A low plasma albumin/globulin ratio, an index of plasma viscosity, was a possible risk factor for ischemic strokes. Urinary albumin/creatinine ratios in the highest quintile increased the risk of stroke 13-fold.

Aged↗
PubMed1990

Biochemical predictors for osteoporotic fractures in elderly Chinese--a longitudinal study.

In a longitudinal study of 283 elderly subjects aged 60 years or over living in the community, 9 subjects (7 women and 2 men) developed osteoporosis-related fractures in 30 months. These subjects initially had higher random urinary hydroxyproline/creatinine and calcium/creatinine ratios, and lower plasma 25-hydroxyvitamin D concentrations. These biochemical variables may be useful predictors of osteoporosis-related fractures and may provide a suitable community screening method to identify those most at risk.

25-Hydroxyvitamin D 2↗
PubMed1990

Acute and long-term changes in serum lipids after acute stroke.

We studied serum lipid profiles in 171 patients less than or equal to 48 hours after the onset of acute stroke and 3 months later. The 83 patients suffering cerebral infarction had significantly higher serum concentrations of total cholesterol, low density lipoprotein-cholesterol, and apolipoprotein B and significantly lower serum concentrations of triglycerides and lipoprotein (a) less than or equal to 48 hours after ictus than 3 months later. The lipid profiles of the 53 patients suffering lacunar infarction were similar on both occasions, the only significant differences being higher total cholesterol and low density lipoprotein-cholesterol concentrations less than or equal to 48 hours after ictus. No significant changes were observed among the 35 patients suffering cerebral hemorrhage apart from a significantly higher concentration of high density lipoprotein3-cholesterol less than or equal to 48 hours after ictus. Our study, with many patients classified according to stroke subtype, gives results different from those of previous studies with much fewer patients. We conclude that in studies of serum lipid and lipoprotein concentrations as risk factors for cerebral infarction, comparing values obtained less than or equal to 48 hours after admission with control values may incorrectly identify certain lipid fractions as risk factors.

Aged↗
PubMed1990

Antigen presentation and HLA-DR expression by FK-506-treated human monocytes.

The novel macrolide immunosuppressant FK-506 demonstrated superior potency to cyclosporin A (CsA) in the inhibition of purified protein derivative (PPD)-induced human T-cell proliferation. Pulsing of monocytes with PPD for 24 hr in the presence of FK-506 did not impair their capacity to subsequently induced the proliferation of purified autologous T cells. In contrast, FK-506 profoundly inhibited the proliferative response of T cells to antigen-pulsed monocytes. Recombinant IL-2, but not IL-1, partially restored the proliferative response to PPD in the presence of the drug. FK-506 had no effect on basal or rIFN-gamma-induced expression of HLA-DR on monocytic cell line cells. These findings provide the first evidence that FK-506 can profoundly inhibit soluble antigen-induced human T-cell proliferation at concentrations which do not significantly impair the accessory function of mononuclear phagocytes.

Anti-Bacterial Agents↗
PubMed1990

A clinical comparison of budesonide nasal aerosol, terfenadine and a combined therapy of budesonide and oxymetazoline in adult patients with perennial rhinitis.

The efficacy of budesonide, terfenadine and a combination of budesonide and oxymetazoline in the treatment of perennial rhinitis was evaluated by a double blind, parallel group study. Adult patients with perennial rhinitis were randomized into three groups. Group 1 patients received budesonide nasal aerosol 400 micrograms/day for 21 days and oxymetazoline nasal drops for the first three days. Group 2 and 3 patients received budesonide 400 micrograms/day and terfenadne tablet 60 mg twice/day respectively. Nasal symptoms were assessed by the patients before and daily during the treatment period using a simple scoring system. One hundred and forty-two patients were recruited and 130 completed the study. Budesonide, but not terfenadine, significantly reduced all nasal symptoms from baseline (p less than 0.05). Terfenadine could significantly relieve the nasal blockage (p less than 0.05) more than other nasal symptoms. Budesonide with or without oxymetazoline nasal drops provided a better control of nasal symptoms than terfenadine (p less than 0.05). Budesonide with oxymetazoline for the first three days showed a faster relief of nasal blockage than budesonide alone (p less than 0.05). Mild and transient adverse effects were encountered in all three groups. It is concluded that nasal symptoms of perennial rhinitis are more adequately controlled by budesonide than by terfenadine.

Adolescent↗