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Biomedical subjects

R J Johnson

Publications and source records attributed to R J Johnson.

At least 19 recordsLinked to original sources
PubMed2006

A "weight-listing" paradox for candidates of renal transplantation?

Research suggests that end-stage renal disease patients with elevated body mass index (BMI) have superior outcomes on dialysis. In contrast, low and high BMI patients represent the highest risk cohorts for kidney transplant recipients. The important question remains concerning how to manage transplant candidates given the potentially incommensurate impact of BMI by treatment modality. We conducted a retrospective analysis of waitlisted and transplanted patients in the United States from 1990 to 2003. We constructed Cox models to evaluate the effect of BMI on mortality of waitlisted candidates and identified risk factors for rapid weight change. We then assessed the impact of weight change during waitlisting on transplant outcomes. Decline in BMI on the waiting list was not protective for posttransplant mortality or graft loss across BMI strata. Substantial weight loss pretransplantation was associated with rapid gain posttransplantation. The highest risk for death was among listed patients with low BMI (13-20 kg/m(2), adjusted hazard ratio = 1.47, p < 0.01). Approximately one-third of candidates had a change in BMI category prior to transplantation. While observed declines in BMI may be volitional or markers of disease processes, there is no evidence that candidates have improved transplant outcomes attributable to weight loss. Prospective trials are needed to evaluate the efficacy of weight loss protocols for candidates of kidney transplantation.

Adolescent↗
PubMed2006

Unearthing uric acid: an ancient factor with recently found significance in renal and cardiovascular disease.

Uric acid is strongly associated with cardiovascular and renal disease, but is usually not considered to have a causal role. However, recent experimental, epidemiological, and clinical studies provocatively suggest that uric acid may contribute to the development of hypertension, metabolic syndrome, and kidney disease in some patients. Clinical studies are urgently needed to examine this important possibility.

Animals↗
PubMed2006

Renal transplantation in Indo-Asian patients in the UK.

Membership of some ethnic groups has an effect on renal transplant outcome but little is known about the impact of Indo-Asian ethnicity, despite this group's high incidence of renal disease. We compared outcomes in Indo-Asians and Caucasians at the Hammersmith Hospital (Indo-Asians, N = 46; Caucasians, N = 90), in the Long-Term Efficacy and Safety Surveillance (LOTESS) database of cyclosporin-treated renal transplant recipients (Indo-Asians, N = 254; Caucasians, N = 4262) and the National Transplant Database held by UK Transplant (Indo-Asians, N = 459; Caucasians, N = 4831). The baseline demographic and co-morbid characteristics of the two ethnic groups were comparable, save for more diabetes in the Indo-Asian community. Following transplantation, the incidence of delayed graft function and steroid-resistant acute rejection were also comparable, as were graft and patient survival (out to 5 years) and graft function. In addition, post-transplant blood pressure, levels of cholesterol and triglycerides and exposure to corticosteroids and cyclosporin were comparable. However, when patients who were not diabetic before transplantation were studied separately, there was an increased incidence of diabetes in the Indo-Asian community (Hammersmith data: Indo-Asians 10.9% vs. Caucasians 3.3%, p = 0.02; LOTESS data Indo-Asians 5.5% vs. Caucasians 1.6%, p < 0.0001). Subsequent management of this group should pursue immunosuppressive regimens less likely to impair post-transplant glucose tolerance.

Adult↗
PubMed2006

A ribonuclease zymogen activated by the NS3 protease of the hepatitis C virus.

Translating proteases as inactive precursors, or zymogens, protects cells from the potentially lethal action of unregulated proteolytic activity. Here, we impose this strategy on bovine pancreatic ribonuclease (RNase A) by creating a zymogen in which quiescent ribonucleolytic activity is activated by the NS3 protease of the hepatitis C virus. Connecting the N-terminus and C-terminus of RNase A with a 14-residue linker was found to diminish its ribonucleolytic activity by both occluding an RNA substrate and dislocating active-site residues, which are devices used by natural zymogens. After cleavage of the linker by the NS3 protease, the ribonucleolytic activity of the RNase A zymogen increased 105-fold. Both before and after activation, the RNase A zymogen displayed high conformational stability and evasion of the endogenous ribonuclease inhibitor protein of the mammalian cytosol. Thus, the creation of ribonuclease zymogens provides a means to control ribonucleolytic activity and has the potential to provide a new class of antiviral chemotherapeutic agents.

Animals↗
PubMed2005

The information needs and preferred roles in treatment decision-making of parents caring for infants with atopic dermatitis: a qualitative study.

BACKGROUND: Information needs and preferences in treatment decision-making of parents caring for infants with atopic dermatitis (AD) are unknown, despite emphasis on quality information-giving and involvement of health-care users in treatment decisions. OBJECTIVE: To explore information needs and decisional role-preferences of parents caring for infants with AD. METHODS: Qualitative study. Purposive sample: 31 parents caring for infants with AD. Tape-recorded focussed conversation-style interviews. Interview topic-guide literature-derived. Control Preferences Scale (5 sort-card vignettes 'very active' to 'very passive' role) adapted for use with parents; used to facilitate discussion. Thematic analysis of verbatim transcripts. RESULTS: Nine core information needs identified: AD-causation, role of diet, medication-use, medication-side-effects, exacerbating factors, new/alternative medication, nonpharmacological treatments, AD-prevention, AD and other atopic conditions. Parents desired verbal and written information. Many felt their baby's condition was not taken seriously, leading to delayed diagnosis and treatment. They had to be more active than they wished to obtain information/treatment. Parents preferred sharing decisions with their doctor. CONCLUSIONS: Parents caring for infants with AD have clearly defined, unmet information needs, forcing them into more active roles in the treatment decision-making process than they desire. The study-findings may inform the development of written information specifically for these parents and improve partnership during consultations.

Adult↗
PubMed2003

PTPRQ is a novel phosphatidylinositol phosphatase that can be expressed as a cytoplasmic protein or as a subcellularly localized receptor-like protein.

PTPRQ (rPTP-GMC1) is a member of the type III receptor-like protein tyrosine phosphatase family. PTPRQ has very low activity against phosphotyrosine but is active against phosphatidylinositol phosphates that are involved in regulation of survival, proliferation, and subcellular architecture. Here, we report that PTPRQ can be expressed as a cytosolic or a receptor-like protein and that the form, subcellular localization, and cell types in which it is expressed are regulated by alternative promoter use and by alternative splicing. The first promoter drives expression of transcripts encoding a transmembrane protein in human podocytes and lung. PTPRQ protein is localized to the basal membrane of human podocytes, beginning when podocyte progenitors can first be identified in the embryonic kidney. A second promoter drives expression of a transcript that can encode a cytoplasmic protein containing the catalytic site. This is the major PTPRQ transcript in rat mesangial cells and human testis and is upregulated in mesangial cells in a rat model of mesangial proliferative glomerulonephritis. Differential regulation of expression of the transmembrane vs cytosolic forms, in different cell types during development or response to injury, may be a mechanism through which PTPRQ, with its activities against membrane phospholipids and against phosphotyrosine, can target specific substrates under different conditions.

Adult↗
PubMed2003

Gastrostomy insertion: comparing the options--PEG, RIG or PIG?

AIM: To compare percutaneous endoscopic gastrostomy (PEG) with radiologically inserted gastrostomy (RIG) and assess a hybrid gastrostomy technique (per-oral image-guided gastrostomy, PIG). MATERIALS AND METHODS: Fifty PEGs and 50 RIGs performed in three centres were prospectively compared and the endoscopic findings of 200 PEGs reviewed. A fluoroscopy-guided technique was modified to place 20 F over-the-wire PEG-tubes in 60 consecutive patients. RESULTS: Technical success was 98%, 100% and 100% for PEG, RIG and PIG, respectively. Antibiotic prophylaxis significantly reduced stoma infection for orally placed tubes (p=0.02). Ten out of 50 (20%) small-bore RIG tubes blocked. Replacement tubes were required in six out of 50 PEGs (12%), 10 out of 50 RIGs (20%), but no PIGs (p<0.001). No procedure-related complications occurred. The function of radiologically placed tubes was significantly improved with the larger PIG (p<0.001), with similar wound infection rates. PIG was successful in 24 patients where endoscopic insertion could not be performed. Significant endoscopic abnormalities were found in 42 out of 200 PEG patients (21%), all related to peptic disease. Insignificant pathology was found in 8.5%. CONCLUSION: PIG combines advantages of both traditional methods with a higher success and lower re-intervention rate. Endoscopy is unlikely to detect clinically relevant pathology other than peptic disease. PIG is a very effective gastrostomy method; it has better long-term results than RIG and is successful where conventional PEG has failed.

Adult↗
PubMed2003

The platelet glycoprotein Ia/IIa gene polymorphism C807T/G873A: a novel risk factor for retinal vein occlusion.

Retinal vein occlusion (RVO) is associated with hyperhomocysteinaemia and the antiphospholipid syndrome-disorders known to contribute to both arterial and venous thrombosis. In both of these conditions and RVO, platelet activation occurs. Aspirin, not warfarin, is the most effective antithrombotic agent in RVO and, taken together, these observations suggest an important role for platelets in this common ocular thrombotic condition. Platelet glycoprotein Ia/IIa (GpIa/IIa) is an adhesion molecule mediating platelet-collagen interactions and is key to the initiation of thrombosis. Recently, the cellular density of this molecule was shown to be determined by two silent, linked polymorphisms (C807T/G873A) within the GpIa/IIa gene. There is evidence that some of the resulting genotypes are associated with thrombo-embolic disease. This study therefore aimed to establish the prevalence of the GpIa/IIa polymorphisms and the three commonest hereditary thrombophilic disorders (prothrombin gene G20210A (PT) mutation, Factor V Leiden (FVL), and the thermolabile methylene tetrahydrofolate reductase C677T (MTHFR) mutation) in patients with RVO and normal controls. The GpIa/IIa polymorphisms and thrombophilic abnormalities were all identified using the polymerase chain reaction.Our results show that the frequency of the GpIa/IIa polymorphisms was similar in our normal control population to previously published series. Patients with RVO, however, had only a 10% (4/40) frequency of the lowest risk subtype (CC/GG) compared to 37.5% (15/40) in the control group-P 0.0039. The incidence of the PT, FVL, and MTHFR thrombophilic mutations was not different between the two groups, but interestingly none of the 7/40 RVO cases with a PT, FVL, or MTHFR mutation had the low-risk GpIa/IIa genotype while all but one of the controls did-P<0.05. Thus, 17.5% of RVO patients harboured more than one prothrombotic abnormality. The principal difference between the RVO and control group was the very high incidence of the intermediate-risk GpIa/IIa subtype (CT/GA)-82.5 vs 50%, P&<0.05. These results suggest a major role for GpIa/IIa polymorphisms in the pathogenesis of RVO.

Adult↗
PubMed2002

Paroxysmal nocturnal haemoglobinuria: nature's gene therapy?

The development of paroxysmal nocturnal haemoglobinuria (PNH) requires two coincident factors: somatic mutation of the PIG-A gene in one or more haemopoietic stem cells and an abnormal, hypoplastic bone marrow environment. When both of these conditions are met, the fledgling PNH clone may flourish. This review will discuss the pathophysiology of this disease, which has recently been elucidated in some detail.

Glycosylphosphatidylinositols↗
PubMed2001

Electrochemistry of chalcogen compounds: prediction of antioxidant activity.

Synthesis and characterisation of organochalcogens has demonstrated a high correlation between their electrochemical oxidation potential on the glassy carbon electrode, their activity in bioassays and an unprecedented antioxidant activity in neuronal cell culture (EC50 approximately 20 nM) making electrochemical methodology a valuable tool in drug design for Alzheimer's and related diseases.

Animals↗
PubMed2001

Hyperuricemia exacerbates chronic cyclosporine nephropathy.

BACKGROUND: Hyperuricemia frequently complicates cyclosporine (CSA) therapy. The observation that longstanding hyperuricemia is associated with chronic tubulointerstitial disease and intrarenal vasoconstriction raised the hypothesis that hyperuricemia might contribute to chronic CSA nephropathy. METHODS: CSA nephropathy was induced by the administration of CSA (15 mg/kg/day) for 5 and 7 weeks to rats on a low salt diet (CSA group). The effect of hyperuricemia on CSA nephropathy was determined by blocking the hepatic enzyme uricase with oxonic acid (CSA-OA). Control groups included rats treated with vehicle (VEH) and oxonic acid alone (OA). Histological and functional studies were determined at sacrifice. RESULTS: CSA treated rats developed mild hyperuricemia with arteriolar hyalinosis, tubular injury and striped interstitial fibrosis. CSA-OA treated rats had higher uric acid levels in association with more severe arteriolar hyalinosis and tubulointerstitial damage. Intrarenal urate crystal deposition was absent in all groups. Both CSA and CSA-OA treated rats had increased renin and decreased NOS1 and NOS3 in their kidneys, and these changes are more evident in CSA-OA treated rats. CONCLUSION: An increase in uric acid exacerbates CSA nephropathy in the rat. The mechanism does not involve intrarenal uric acid crystal deposition and appears to involve activation of the renin angiotensin system and inhibition of intrarenal nitric oxide production.

Animals↗
PubMed2001

The effect of weightbearing and external loading on anterior cruciate ligament strain.

A force balance between the ligaments, articular contact, muscles and body weight maintains knee joint stability. Thus, it is important to study anterior cruciate ligament (ACL) biomechanics, in vivo, under weightbearing conditions. Our objective was to compare the ACL strain response under weightbearing and non-weightbearing conditions and in combination with three externally applied loadings: (1) anterior-posterior shear forces, (2) internal-external torques, and (3) varus-valgus moments. A strain transducer was implanted on the ACL of 11 subjects. All joint loadings were performed with the knee at 20 degrees of flexion. A significant increase in ACL strain was observed as the knee made the transition from non-weightbearing to weightbearing. During anterior shear loading, the strain values produced during weightbearing were greater than those of the non-weightbearing knee (shear loads <40N). At higher shear loads, the strain values became equal. During axial torsion, an internal torque of 10Nm strained the ACL when the knee was non-weightbearing while an equivalent external torque did not. Weightbearing significantly increased ACL strain values in comparison to non-weightbearing with the application of external torques and low internal torques (<3Nm). The strains became equal for higher internal torques. For V-V loading, the ACL was not strained in the non-weightbearing knee. However, weightbearing increased the ACL strain values over the range of moments tested. These data have important clinical ramifications in the development of rehabilitation protocols following ACL reconstruction since weightbearing has been previously thought to provide a protective mechanism to the healing graft.

Adult↗
PubMed2001

The gastrocnemius muscle is an antagonist of the anterior cruciate ligament.

Since the proximal tendon of the gastrocnemius muscle wraps around the posterior aspect of the tibia, its contraction could potentially strain the anterior cruciate ligament (ACL) by pushing the tibia anteriorly. However, the relationship between contraction of the gastrocnemius muscle and ACL strain has not been studied in vivo. The objectives of this study were to evaluate the ACL strain response due to isolated contractions of the gastrocnemius muscle and to determine how these strains are affected by cocontraction with the hamstrings and quadriceps muscles. Six subjects with normal ACLs participated in the study; they underwent spinal anesthesia to ensure that their leg musculature was relaxed. Transcutaneous electrical muscle stimulation (TEMS) was used to induce contractions of the gastrocnemius, quadriceps and hamstrings muscles while the strains in the anteromedial bundle of the ACL were measured using a differential variable reluctance transducer. The ACL strain values produced by contraction of the gastrocnemius muscle were dependent on the magnitude of the ankle torque and knee flexion angle. Strains of 2.8% and 3.5% were produced at 5 degrees and 15 degrees of knee flexion, respectively. The ACL was not strained at 30 degrees and 45 degrees. Changes in ankle angle did not significantly affect these strain values. Co-contraction of the gastrocnemius and quadriceps muscles produced ACL strain values that were greater than those produced by isolated activation of either muscle group when the knee was at 15 degrees and 30 degrees. Co-contraction of the gastrocnemius and hamstrings muscles produced strains that were higher than those produced by the isolated contraction of the hamstrings muscles. At 15 degrees and 30 degrees of knee flexion. the co-contraction strain values were less than those produced by stimulation of the gastrocnemius muscle alone. This study verified that the gastrocnemius muscle is an antagonist of the ACL. Since the gastrocnemius is a flexor of the knee, this finding may have important clinical ramifications in ACL rehabilitation since flexor torques are generally thought to be protective of a healing ACL graft.

Adult↗