Inhibition of the human antipig xenograft reaction with soluble oligosaccharides.
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ABO Blood-Group System↗
Biomedical subjects
T Cook
Publications and source records attributed to T Cook.
Primary care to the underserved through community empowerment.
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Community Participation↗
Expression and functional characterisation of a synthetic version of the human D4 dopamine receptor in a stable human cell line.
A synthetic version of the human D4 (hD4) dopamine receptor was prepared. The G/C content of the natural gene was reduced by 14% without altering the amino acid composition of the corresponding protein sequence. HEK293 cells were transfected with the synthetic hD4 gene and stable clones resistant to G418 selected. The hD4 receptor expressed from the synthetic gene had identical pharmacological characteristics to the native hD4 receptor [(1991) Nature 350, 610-619; (1992) Nature 358, 149-152]. Functional studies with cells expressing the synthetic hD4 gene indicated negative coupling of this receptor to adenylate cyclase.
Adenylyl Cyclases↗
Pretreatment of renal transplants with anti-CD45 antibodies: optimization of perfusion technique.
Pig kidneys were perfused ex vivo with a monoclonal anti-pig CD45 antibody to determine optimum conditions for human kidney anti-CD45 perfusion, as such pretreatment may prolong renal allograft survival. Efficacy of perfused antibody uptake was assessed by immunohistochemical double-labelling of multiple renal biopsies. Antibody uptake by CD45+ cells was rapid, and maximal within one hour of perfusion. An antibody concentration of 40 micrograms/ml more effectively saturated available CD45 binding sites than lower concentrations. Whilst cortical perfusion was homogeneous (median uptake > 99%, minimum 90.0%) after 25, 50 or 100 ml perfusion with 40 micrograms/ml monoclonal antibody (mAb), the medulla was less evenly perfused with 25 ml (median uptake 82.6%) than with 50 or 100 ml (median uptake 98.5% and 98.7%, respectively). Prolongation of renal cold ischaemia of up to 46 hours prior to mAb perfusion did not adversely affect antibody binding. Clamping of the renal vein during and after mAb perfusion was associated with better cortical and medullary mAb uptake than if the vein was left unclamped. These data show that the vast majority of the kidney's CD45+ antigen-presenting cells can be bound by anti-CD45 mAb perfused ex vivo, if an adequate volume and concentration of mAb perfusate is employed and the renal vein is clamped during and after the process.
Animals↗
Effect of finasteride on prostate-specific antigen density.
OBJECTIVE: Prostate-specific antigen density (PSAD) has been proposed as a diagnostic marker for prostate cancer. Because treatment with finasteride may affect PSAD differently in men with BPH compared with men with BPH plus prostate cancer, we evaluated the diagnostic utility of PSAD in men treated with finasteride for twelve months. METHODS: Data for this analysis were obtained from 895 men with BPH enrolled in a twelve-month placebo-controlled North American study. Prostate volume was measured by magnetic resonance imaging and PSA was measured by the Hybritech immunoradiometric assay. RESULTS: Treatment with finasteride for twelve months increased the positive predictive value of PSAD for identifying the presence of prostate cancer from 14 percent to 30 percent. Using PSA values alone with a cutoff of 10 ng/mL at baseline and 5 ng/mL after twelve months of treatment, similar specificity and sensitivity could be achieved. CONCLUSION: The data suggest that adjustment of PSA values during treatment with finasteride can be used to maintain the diagnostic accuracy for prostate cancer while PSAD can be used to provide additional reassurance without requiring adjustment for treatment.
Adult↗
Induction of nitric oxide synthase in rat immune complex glomerulonephritis.
Nitric oxide (NO) is a biological mediator which is synthesized from L-arginine by a family of nitric oxide synthases (NOS). Previously we have shown that NO is synthesized ex vivo by glomeruli obtained from animals with acute immune complex glomerulonephritis. We have now sought evidence for the in vivo induction of NOS in glomeruli by immunohistochemistry using specific antisera raised against a peptide sequence of inducible mouse macrophage NOS and by in situ hybridization. The expression of the enzyme was studied in kidneys of rats with acute unilateral immune complex glomerulonephritis, induced by cationized IgG, by immunohistochemistry. Inducible NOS (iNOS) was present in glomeruli in nephritic (left) kidneys at the time of maximum macrophage infiltration, both within intraglomerular mononuclear cells and cells emigrating into Bowman's space. iNOS expressing cells were also present in interstitial infiltrates. There was no expression in normal rat kidneys or in glomeruli in the non-nephritic (right) kidneys of experimental rats. In situ hybridization confirmed the immunohistochemical localization. These results provide the first direct evidence for the presence and localization of inducible NOS in glomeruli and support a significant role for NO in the pathogenesis of immune complex glomerulonephritis.
Amino Acid Oxidoreductases↗
Glomerular expression and cell origin of transforming growth factor-beta 1 in anti-glomerular basement membrane disease.
The glomerular expression (mRNA levels) of transforming growth factor-beta 1 (TGF-beta 1) was assessed in two forms of rat anti-glomerular basement membrane (GBM) disease, a macrophage-independent and a macrophage-dependent variant. After a single intravenous injection of rabbit anti-rat GBM immune serum, significant proteinuria and histopathologic changes developed in both variants. Increased TGF-beta 1 mRNA levels were found in isolated glomeruli of the macrophage-dependent variant only in which glomerular infiltration by macrophages also occurred. Macrophages isolated from glomeruli of animals with this variant demonstrated TGF-beta 1 mRNA levels comparable to those found in glomeruli isolated at the same time point after injection of the anti-GBM serum. The observations indicate that in anti-GBM disease, enhanced glomerular TGF-beta 1 expression occurs in the macrophage-dependent variant and suggest that infiltrating macrophages account for this event.
Animals↗
Bronchospasm and the laryngeal mask airway.
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Adult↗
Proliferating cell nuclear antigen (PCNA) as a diagnostic marker of acute cellular rejection in routinely processed biopsies of renal allografts.
Seventy-eight renal allograft biopsies taken for the management of graft dysfunction were analysed retrospectively by labelling with antibodies to proliferating cell nuclear antigen (PCNA) to assess whether this marker could distinguish episodes of rejection. Routinely processed, paraffin-embedded biopsies with focal or diffuse cellular infiltrates were selected and the percentage of infiltrating cells in the cortical interstitium which stained with PCNA antibody were counted (PCNA index). The area of cellular infiltration was also estimated by a morphometric point-counting technique. The biopsies were divided into two groups based on standard clinical criteria; those with acute rejection (n = 31) and those with other causes of graft dysfunction (n = 47). The PCNA index was significantly higher in episodes of acute rejection (7.9%) compared to non-rejection (2.1%). This was independent of time after transplantation. The PCNA index was also greater in rejecting kidneys containing only focal cellular infiltrates (percentage area of cellular infiltration < 13.1%). Thus PCNA staining may be of use in the differential diagnosis of rejection in routinely processed biopsies of renal allografts where there are only focal inflammatory infiltrates, otherwise not diagnostic of cellular rejection.
Acute Disease↗
Maximum urinary flow rate by uroflowmetry: automatic or visual interpretation.
We measured the maximum urinary flow rate monthly for 1 year by uroflowmetry in 1,645 patients in a double-blind, placebo-controlled study of finasteride therapy for benign prostatic hyperplasia. Patients were randomized to receive placebo (555) or finasteride (1,090). A total of 23,857 flow measurements was obtained. Because of the presence of artifacts on many uroflow curves, we read the maximum urinary flow rate values manually and compared them to the values provided electronically by the uroflowmeter. On average, the manually read values were 1.5 ml. per second lower than the machine read values. Artifacts causing a difference of 2 ml. per second or more between the 2 methods were found in 20% and of more than 3 ml. per second in 9% of the tracings. The difference between treatment groups in mean maximum urinary flow rate change at the end of the study was the same with both reading methods. However, confidence intervals were 15 to 25% larger for the machine read compared to the manually read values. This larger variability in machine read maximum urinary flow rate has a marked negative impact on the power of statistical tests to assess any given difference in maximum urinary flow rate between treatment groups. Furthermore, it increases sample size requirements by 50% to achieve any given statistical power. We conclude that maximum urinary flow rate artifacts contribute significantly to the variability of maximum urinary flow rate measurement by uroflowmetry. Manual reading of the maximum urinary flow rate eliminates an important fraction of such variability.
5-alpha Reductase Inhibitors↗
Renal function and biopsy findings after 5 years' treatment with low-dose cyclosporin for psoriasis.
Renal biopsies were performed in eight patients with chronic plaque psoriasis who had been treated with low-dose cyclosporin (CyA) (range 1-6 mg/kg/day; average dose 3.3 mg/kg/day) for an average period of 5 years. In six of the eight patients biopsies showed features consistent with CyA nephrotoxicity. Tubular atrophy and arteriolar hyalinosis were present in all six, four had an increase in interstitium, and two showed an increased incidence of glomerular obsolescence. Two of the patients showed all of these features, two patients had three features, and the remaining patients had two features. Renal function was assessed by glomerular filtration rate (GFR) and serum creatinine. Both a fall in the GFR and a rise in the serum creatinine correlated with the severity of the features of CyA nephrotoxicity seen on biopsy. However, the best predictor of the biopsy findings was a failure of renal function to show significant improvement when CyA was discontinued for a month. CyA has been discontinued in two of the eight patients who had the most severe features of CyA nephrotoxicity on renal biopsy. In both patients there has been improvement of renal function after 1 year of follow-up.
Adult↗
"Pneumo-ptosis" in the emergency department.
The authors report the case of a 16-year-old female who presented with a left tension pneumothorax and a left Horner's syndrome. Chest tube thoracostomy performed to relieve the tension pneumothorax also resulted in the immediate resolution of the patient's ptosis and miosis. The probable mechanism for the patient's focal neurologic signs was traction upon the cervical sympathetic chain secondary to the mediastinal shift of the tension pneumothorax. This case demonstrates that unequal pupils in the presence of a pneumothorax could represent Horner's syndrome.
Adolescent↗
The safety and efficacy of topical norfloxacin compared with chloramphenicol for the treatment of external ocular bacterial infections. The Norfloxacin-Chloramphenicol Ophthalmic Study Group.
Two hundred and forty-six patients with signs of acute bacterial conjunctivitis and/or blepharitis were randomised to receive either norfloxacin or chloramphenicol for one week in this double-masked parallel group study. Ninety-two per cent of the norfloxacin-treated patients and 93% of the chloramphenicol-treated patients were rated as either clinically improved or cured at the end of the treatment period. Based upon pre-treatment bacteriological cultures, 31.3% of the patients had significant bacterial infection of the lids and/or conjunctiva. All of these culture-positive patients were rated as either clinically improved or cured. Based upon post-treatment cultures, 72 of 82 strains of Gram-positive and Gram-negative bacteria were eradicated or suppressed following treatment with either norfloxacin or chloramphenicol. However six of 41 strains persisted for norfloxacin and four of 41 for chloramphenicol. Two norfloxacin-treated patients and three chloramphenicol-treated patients had adverse experiences, predominantly ocular discomfort, which required cessation of drug therapy. Norfloxacin appears to be an effective and relatively safe agent for the treatment of bacterial infections of the lids and/or conjunctiva. In this study, norfloxacin was clinically and microbiologically similar in activity to chloramphenicol.
Acute Disease↗
Urinary excretion of nitrite and nitrate in experimental glomerulonephritis reflects systemic immune activation and not glomerular synthesis.
In immune-induced glomerulonephritis (gn), glomeruli (gl) synthesize nitric oxide (NO), and urinary nitrite (NO2-) excretion is increased. In mammals on a low nitrate (NO3-) diet, urinary NO3- is a measure of endogenous NO3- synthesis. Excretion is increased after administration of macrophage activators, reflecting induction of NO production. To determine whether increased urinary NO2- gn is due to glomerular synthesis we studied urinary NO2-/NO3- in accelerated nephrotoxic nephritis induced by preimmunization with rabbit immunoglobulin G (IgG), followed by rabbit anti-rat nephrotoxic globulin, and in control rats similarly preimmunized with rabbit IgG, but followed by normal rabbit serum. Both urinary NO2- and NO3- were increased by i.p. preimmunization with rabbit IgG (peak 463 +/- 171 nmol NO2-/60.3 +/- 9.4 nmol NO3-/24 h, P < 0.001 for both NO2- and NO3- compared with preimmunization levels). Repeat immunization with i.v. rabbit anti-rat nephrotoxic globulin (nephritic rats) or normal rabbit globulin (control rats) again increased urinary NO2- and NO3-. There was no statistically significant difference in urinary NO2- and NO3- levels between nephritic rats where globulin had nephrotoxic activity and the control rats injected with normal rabbit globulin, despite increased NO2- synthesis in ex vivo nephritic glomeruli after nephrotoxic globulin (7.9 +/- 1.9 nmol/2000 gl/48 h; controls 3.2 +/- 1.0 nmol/2000 gl/48 h). Thus neither urinary NO2- nor NO3- levels reflect local activation of the NO pathway in glomeruli. As reported for other stimulants, we show here that systemic stimulation with foreign antigen increased NO synthesis.
Animals↗
Nocardia infection in AIDS: a clinical and microbiological challenge.
A case of Nocardia asteroides pneumonia was diagnosed after death in a patient with AIDS. Six sputum cultures and one bronchoalveolar lavage fluid contained no pathogens, and no growth was obtained from one pleural fluid aspirate. None of these specimens was incubated for more than two days. Extended incubation for mycobacteria also failed to help in the diagnosis. N asteroides was isolated from pus taken from the lung cavity during the post mortem examination. It is suggested that if nocardiosis enters the differential diagnosis all specimens should be cultured for at least two weeks and the use of selective media be considered. This case highlights the need for clinicians to maintain a high index of suspicion for this pathogen.
Acquired Immunodeficiency Syndrome↗
Observer variability in the radiographic measurement and classification of metatarsus adductus.
The classification system of Berg was evaluated using four observers and the radiographs of 42 feet from patients with metatarsus adductus. Interobserver disagreement in diagnosis was 36%. Intraobserver inconsistency averaged 26%. The error range for the lateral and anteroposterior talocalcaneal angle measurement was 13.6 and 15.1 degrees intraobserver and 19.8 and 25.2 degrees interobserver, respectively. There was no correlation between classification and the length of time required for cast correction. The irregularity of hindfoot ossification centers makes measurements inconsistent and seriously reduces the usefulness of classification based on such measurements.
Child↗
Glomeruli synthesize nitrite in active Heymann nephritis; the source is infiltrating macrophages.
Glomeruli synthesize nitrite (NO2-) in experimental nephrotoxic nephritis, a model of glomerulonephritis where infiltrating macrophages are pathogenic. NO2- synthesis was studied in active Heymann nephritis (AHN), a model of membranous glomerulonephritis in which macrophages have not been implicated. Active Heymann nephritis (AHN) was induced with purified renal tubular epithelial antigen and adjuvants. Glomeruli isolated at seven to eight weeks after induction (proteinuria 183 +/- 28 mg/24 hr, N = 6; adjuvant controls, 1.2 +/- 0.8 mg/24 hr, N = 6) produced NO2- in culture spontaneously (7.1 +/- 1.4, adjuvant controls 2.1 +/- 0.9 nmol/2000 g/48 hours; P = 0.021) and in increased amount following LPS stimulation (12.1 +/- 2.8, controls 4.2 +/- 1.6 nmol/2000 g/48 hours; P = 0.047). Synthesis was inhibited by L-NMMA, a competitive inhibitor of NO synthase. Enzymic digestion of glomeruli plus staining with mouse anti-rat macrophage monoclonal antibody ED1 showed macrophage infiltration (32 +/- 6, adjuvant controls 14 +/- 2 macrophages/glomerulus; P = 0.002). Whole body irradiation (XR) suppressed NO2- production (LPS stimulated: 1.0 +/- 0.4, N = 5; non-XR controls 7.2 +/- 4.6 nmol/2000 g/48 hours; N = 5, P = 0.016) and macrophage infiltration (1.1 +/- 0.5; non-XR controls 30 +/- 12 macrophages/glomerulus; P = 0.008) but had no effect on proteinuria. Irradiation with renal shielding confirmed the close correlation between glomerular NO2- synthesis and glomerular macrophage numbers (rs = 0.837, P less than 0.001). These results show that macrophages infiltrate glomeruli in AHN; they are the source of NO2- in this model. Neither macrophages nor NO2- are the cause of proteinuria.
Animals↗
Glomeruli synthesize nitrite in experimental nephrotoxic nephritis.
Activated macrophages synthesize nitric oxide (NO) from L-arginine. In culture, the major stable end product is nitrite (NO2). Activated macrophages accumulate in glomeruli and are responsible for injury in experimental immune complex glomerulonephritis. We examined NO2- production by isolated glomeruli and urinary NO2- in accelerated nephrotoxic nephritis in the rat. Normal glomeruli did not produce NO2- spontaneously or when stimulated with lipopolysaccharide (LPS) (1 microgram/ml) or A23187 (2 microgram/ml). Cultured mesangial cells at first or seventh passage did not produce NO2- spontaneously or when stimulated. Nephritic glomeruli spontaneously produced NO2 at all times studied; this production was maximal at 24 hours after induction of glomerulonephritis (158.4 +/- 8.4 nmol/48 hr/ml, N = 3). The production of NO2- was inhibited 75 to 100% by NG-monomethyl-L-arginine (L-NMMA), and this inhibition was reversed by L-arginine, indicating NO2- production from L-arginine via NO. The production of NO2- was increased by LPS (1 microgram/ml) at 2, 7 and 21 days. NO2- was undetectable in normal rat urine; however, it was present in urine of rats with glomerulonephritis (Day 0 to 1:8161 +/- 2605 nmol/24 hr. N = 12). The production of NO in nephritic glomeruli may have implications for both the mechanism of glomerular injury and glomerular hemodynamics.
Animals↗