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Biomedical subjects

M L Nicholson

Publications and source records attributed to M L Nicholson.

At least 145 records · Page 8Linked to original sources
PubMed1996

Formation and cell-medium partitioning of autoinhibitory free fatty acids and cyclodextrin's effect in the cultivation of Bordetella pertussis.

Palmitic, palmitoleic and stearic acids were found in the extracted cellular lipids of virulent Bordetella pertussis as unesterified acids in confirmation of earlier taxonomic analyses. The same free fatty acids (FFAs) were found in the spent culture supernatant in concentrations higher than in the uninoculated medium, indicating that they are released into the extracellular medium. These long-chain fatty acids are known to inhibit the growth of B. pertussis at concentrations as low as 1 ppm. Measurement of palmitate cell-medium partitioning demonstrated a strong tendency of FFAs for cellular adsorption. Inhibition kinetics indicated that the cell-bound FFA was responsible for inhibition and that the specific cellular FFA concentrations actually found during growth were similar to those determined to be inhibitory. Autoinhibition by these endogenous FFAs provides an explanation of the low maximum cell concentrations currently attainable in liquid media. Addition of soluble dimethyl-beta-cyclodextrin (MebetaCD) to FFA-inhibited cultures resulted in a rapid reversal of the inhibition. A corresponding shift in the distribution of FFAs from the cells to the extracellular medium demonstrated that MebetaCD sequesters FFAs. Although MebetaCD did not increase final cell concentrations and even had an adverse effect on growth at concentrations above 1 g l-1, it did (at 1 g l-1 extend the initial period of high growth rate leading to shorter cultivation times.

Biotechnology↗
PubMed1996

Early measurement of interstitial fibrosis predicts long-term renal function and graft survival in renal transplantation.

This study investigated the relationships between renal allograft interstitial fibrosis, renal function and graft survival. A total of 107 consecutive renal transplant recipients immunosuppressed with cyclosporin were studied. Needle core transplant biopsies were performed before operation and at 1, 6 and 12 months after transplantation. Allograft fibrosis was assessed by histomorphometric analysis of graft interstitial volume fraction. Renal function was measured by isotopic glomerular filtration rate (GFR) measurement at the same time points. Interstitial volume fraction was already high in preperfusion biopsies, significantly increased with time but stabilized at 6 months after transplantation. GFR correlated negatively with interstitial volume fraction at 6 months (P = 0.05). Interstitial volume fraction at 1 month was not a useful predictor of subsequent graft survival but for allografts surviving to 6 months an interstitial volume fraction above 25 per cent predicted significantly poorer survival (P = 0.04). It provides an objective measure of chronic allograft damage and may prove to be a useful surrogate endpoint in the study of therapeutic intervention.

Biopsy, Needle↗
PubMed1996

Work-load generated by the establishment of a non-heart beating kidney transplant programme.

The work-load generated by a non-heart-beating donor (NHBD) kidney transplant programme over a 3-year period is reported. A total of 73 referrals were made, 64 from the Accident department and 9 from the wards. Organ procurement was performed in 24 cases (33%) and resulted in the retrieval of 44 kidneys. Reasons for failure to achieve organ procurement were; refused consent (n = 13; 18%), relatives unavailable to ask for consent (n = 9; 12%), technical problems with catheter insertion or perfusion (n = 10; 14%), transplant staff unavailable (n = 1; 1%), long asystolic period (n = 8; 11%) and donor unsuitable for other reasons (n = 8; 11%). Of the 44 kidneys retrieved, 30 were transplanted locally, 8 were transplanted at other United Kingdom centres and 6 were discarded. Locally transplanted NHBD kidneys represented 21% of the total transplant programme during the time period under study. We conclude that NHBD kidneys are a good source of additional organs for transplantation, but only one-third of referrals result in a successful procurement procedure. Moreover, the setting up of a successful programme is labour-intensive and requires a highly committed staff.

Humans↗
PubMed1996

The relative influence of delayed graft function and acute rejection on renal transplant survival.

Three hundred and eight cadaveric renal transplants were analysed to establish the effects of acute rejection in the first 90 days and delayed graft function (DGF) on graft outcome. There were 120 patients (39%) with no DGF and no rejection (group 1), 101 patients (33%) with rejection but no DGF (group 2), 41 patients (13%) with DGF but no rejection (group 3) and 46 patients (15%) with both rejection and DGF (group 4). The actuarial 4-year graft survival rates for groups 1,2,3 and 4 were 78.3%, 65.4%, 60.1% and 40.4%, respectively. The acute rejection rate was 101/221 (46%) in patients with initial graft function compared with 46/87 (53%) for those with DGF (chi 2 = 1.02, P = 0.31). Cox stepwise logistic regression analysis demonstrated that DGF was a more powerful predictive factor for poor graft survival (P = 0.001) than acute rejection occurring in the first 90 days post-transplant (P = 0.034). Further efforts at improving graft outcome should concentrate on reducing the incidence of DGF.

Acute Disease↗
PubMed1996

A prospective randomised study of the effect of nicardipine on ischaemic renal injury in renal allografts.

In a prospective double-blind trial, 127 kidneys were randomised to receive Eurocollins (n = 65) or Eurocollins plus nicardipine (n = 62) as a second flush solution at the time of organ retrieval. Delayed graft function occurred in 18 of 65 control kidneys (28%) and in 20 of 62 nicardipine kidneys (32%; P = 0.7, Fischer's exact test). The mean (SD) serum creatinine at 6 weeks was 197 (138) mumol/l in the Eurocollins group and 195 (159) mumol/l in the nicardipine group (P = 0.95). Eighteen recipients (28%) in the controlled Eurocollins group experienced a rejection episode in the first 6 weeks post-transplant compared to 17 (27%) in the nicardipine group (chi 2 with Yates' correction = 0.027; P = > 0.95). In this study, the addition of nicardipine to the kidney perfusion fluid did not have a beneficial effect on kidney function following transplantation.

Adolescent↗
PubMed1996

Renal ischaemia--reperfusion injury.

Ischaemia-reperfusion injury is a complex interrelated sequence of events that classically involves the vascular endothelium and activated leucocytes. During the ischaemic phase the endothelium is primed both to produce free radicals and to secrete chemoattractants. The resultant neutrophil sequestration serves to amplify the injury, but damage is not confined to the postischaemic area and more generalized effects typically follow. The situation in the kidney is complex for, while ischaemia primes the tissue for reperfusion damage, it also causes early and irreversible tubular injury. Furthermore, it appears that relatively less importance should be attached to the involvement of neutrophils than at other sites, and relatively more to a local postischaemic imbalance in the levels of nitric oxide and endothelin. Despite a greater understanding of the pathogenesis of ischaemia-reperfusion injury, effective treatment remains elusive and research is hampered by apparent species and organ-specific differences.

Free Radicals↗
PubMed1996

Randomized controlled trial of the effect of mannitol on renal reperfusion injury during aortic aneurysm surgery.

The effects of mannitol on renal impairment following infrarenal aortic aneurysm repair were studied. Patients received either mannitol 0.3 g/kg (n = 15) or saline (n = 13) as a rapid intravenous infusion before aortic cross-clamping. One patient in the control group developed fatal postoperative renal failure but there was no renal failure in the mannitol group. Two patients treated with mannitol died from perioperative myocardial infarction. There were no significant differences in postoperative blood urea level, serum creatinine concentration or creatinine clearance between mannitol and control groups. In patients who had mannitol there was a significant diuresis on the first day after operation (mean urine output 2250 ml) compared with before operation (1557 ml) (P = 0.007). Compared with controls, patients treated with mannitol had lower mean (s.e.m.) postoperative levels of urinary albumin (160(32) versus 500(140) mg per mmol creatinine; P = 0.036) and N-acetyl glucosaminidase (143(34) versus 271(70) mumol per mmol creatinine; P = 0.04) indicating a reduced level of subclinical glomerular and renal tubular damage. These data demonstrate that mannitol reduces subclinical renal injury following infrarenal aortic aneurysm repair.

Aged↗
PubMed1996

Parathyroidectomy in chronic renal failure: comparison of three operative strategies.

The efficacy of subtotal parathyroidectomy (n = 11), total parathyroidectomy+autotransplantation (n = 13) and total parathyroidectomy alone (n = 24) were compared in a series of renal patients with hyperparathyroidism. The principal indication for surgery was severe bone disease but other indications were uncontrolled hypercalcaemia, soft tissue calcification and grossly elevated parathyroid hormone (PTH) levels. The clinical success rates at 24 months follow-up for subtotal, total plus autograft, and total parathyroidectomy were 100, 89 and 97% respectively. Similar improvements in radiological changes and alkaline phosphatase levels were seen in all three groups. Recurrent hyperparathyroidism was recorded in three (27%) members of the subtotal parathyroidectomy group and two (16%) of the patients undergoing total parathyroidectomy and autotransplantation. Two patients required re-exploration of their forearm parathyroid autograft. No patients undergoing total parathyroidectomy only suffered persistent or recurrent hypercalcaemia. Vitamin D analogue requirements rates in patients undergoing subtotal, total plus autotransplant, and total parathyroidectomy at 24 months were 44, 70 and 81% respectively. An important finding is the demonstration of residual parathyroid function in 14/16 patients (87.5%) undergoing total parathyroidectomy without autotransplantation and followed-up for 2 years.

Bone Diseases↗
PubMed1995

Two enzymes together capable of cysteine biosynthesis are encoded on a cyanobacterial plasmid.

The cyanobacterium Synechococcus sp. PCC 7942 contains two endogenous, genetically cryptic plasmids of 8.0 and 48.5 kb, which have been designated pANS and pANL, respectively. Characterization of the 3.8 kb Ba6 BamHI fragment of pANL identified three open reading frames which were transcriptionally regulated by sulfur availability and the protein CysR. One of these genes, designated srpG, encodes a protein which exhibits 67% amino acid identity to the Escherichia coli enzyme O-acetyl-L-serine (thio)-lyase A. Overlapping the 3' end of srpG is a second gene, designated srpH, which encodes a protein with similarity to the amino-terminal region of serine acetyltransferase enzymes. DNA hybridization results indicate that there is second copy of srpG in Synechococcus sp. PCC 7942, which is consistent with previous isoenzyme studies on O-acetyl-L-serine (thiol)-lyase in cyanobacteria. The introduction of srpG and srpH into E. coli cysKcysM and cysE mutant strains, respectively, results in the complementation of the lesion in cysteine biosynthesis. Additionally, the E. coli cysK cysM strain containing srpG is able to utilize sulfate more efficiently than thiosulfate, indicating that SrpG is probably a type A O-acetyl-L-serine (thiol)-lyase. The possible function of these genes in the adaptation of cyanobacteria to sulfur stress is discussed.

Acetyltransferases↗
PubMed1995

Genes encoded on a cyanobacterial plasmid are transcriptionally regulated by sulfur availability and CysR.

A cyanobacterial sulfur-regulated gene (cysR), which encodes a protein with similarity to the Crp family of prokaryotic regulatory proteins, has recently been isolated and characterized. Polyacrylamide gel electrophoresis of periplasmic protein extracts reveals that a cysR mutant fails to synthesize a 36-kDa polypeptide that is normally induced in wild-type cells that have been grown under sulfur-deficient conditions. The amino-terminal sequence of this protein was obtained, and a synthetic oligonucleotide was used to isolated a clone containing a 1.9-kb NruI-KpnI fragment from a Synechococcus sp. strain PCC 7942 genomic library. RNA blot analysis indicates that this fragment encodes a transcript that is detectable in wild-type but not cysR mutant cells that have been starved for sulfur. DNA blot analysis revealed that the 1.9-kb NruI-KpnI fragment is contained within the Ba4 BamHI fragment of the endogenous 50-kb plasmid pANL. RNA blot studies indicate that the accumulation of a large number of pANL transcripts is regulated by sulfur levels and CysR. DNA sequence analysis confirmed that the gene encoding the sulfur-regulated 36-kDa periplasmic protein is encoded on the Ba4 fragment of pANL. The sequence of the 36-kDa protein displays sequence similarity to the enzyme catalase, and two downstream proteins exhibit 25 and 62% identity to a subunit of a P-type ATPase complex involved in Mg2+ transport and a chromate resistance determinant, respectively. Surprisingly, a strain in which the putative chromate resistance gene was interrupted by a drug resistance marker exhibited increased resistance to chromate when grown in media containing low sulfate concentrations. The possible role of this protein in the acclimation of cyanobacteria to conditions of low sulfur availability is discussed.

Amino Acid Sequence↗
PubMed1995

An audit of fatal acute pancreatitis.

Acute pancreatitis has a mortality of about 10%: this figure has not changed over the last 20 years. A retrospective audit of fatal acute pancreatitis was performed in a teaching hospital with a catchment population of about 750,000 patients to examine patient characteristics. Using Hospital Activity Analysis code 577.0, all fatal cases of acute pancreatitis were studied in a six-year period 1987-93. Additionally, all post mortem diagnoses of acute pancreatitis were traced. The overall post mortem rate in Nottingham at the time of the study was about 35%. All available records, X-ray and biochemical data were studied and appropriate information recorded and analysed for 65 fatal cases. Only 15% were post mortem diagnoses, lower than in previous series; 72% had respiratory and 67% had renal complications. Only 34% had been admitted to the intensive care unit. A third of patients had had surgery; 67% of these was some form of external drainage. Of the 14 patients with proven gallstone pancreatitis only three had endoscopic retrograde cholangiopancreatography; 42% of patients had idiopathic disease. Not all the patients diagnosed ante mortem had the full biochemical predicted severity criteria analysed: pO2 and calcium analysis was performed in about 80%. Pre-mortem diagnoses of pancreatitis was achieved more frequently than in other comparable series.

Acute Disease↗